StemCell Therapy

When it comes to Alzheimers versus science, science is on the losing side.

Alzheimers is cruel in the most insidious way. The disorder creeps up in some aging brains, gradually eating away at their ability to think and reason, whittling down their grasp on memories and reality. As the worlds population ages, Alzheimers is rearing its ugly head at a shocking rate. And despite decades of research, we have no treatmentnot to mention a cure.

Too much of a downer? The National Institutes of Health (NIH) agrees. In one of the most ambitious projects in biology, the NIH is corralling Alzheimers and stem cell researchers to come together in the largest genome editing project ever conceived.

The idea is simple: decades of research have found certain genes that seem to increase the chance of Alzheimers and other dementias. The numbers range over hundreds. Figuring out how each connects or influences anotherif at alltakes years of research in individual labs. What if scientists unite, tap into a shared resource, and collectively solve the case of why Alzheimers occurs in the first place?

The initiatives secret weapon is induced pluripotent stem cells, or iPSCs. Similar to most stem cells, they have the ability to transform into anythinga cellular Genie, if you will. iPSCs are reborn from regular adult cells, such as skin cells. When transformed into a brain cell, however, they carry the original genes of their donor, meaning that they harbor the original persons genetic legacyfor example, his or her chance of developing Alzheimers in the first place. What if we introduce Alzheimers-related genes into these reborn stem cells, and watch how they behave?

By studying these iPSCs, we might be able to follow clues that lead to the genetic causes of Alzheimers and other dementiaspaving the road for gene therapies to nip them in the bud.

The iPSC Neurodegenerative Disease Initiative (iNDI) is set to do just that. The project aims to stimulate, accelerate, and support research that will lead to the development of improved treatments and preventions for these diseases, the NIH said. All resulting datasets will be openly shared online, for anyone to mine and interpret.

In plain language? Lets throw all of our new biotech superstarswith CRISPR at the forefrontinto a concerted effort against Alzheimers, to finally gain the upper hand. Its an Avengers, assemble moment towards one of our toughest foesone that seeks to destroy our own minds from within.

Alzheimers disease was first recognized in the early 1900s. Ever since, scientists have strived to find the cause that makes a brain waste away.

The most prominent idea today is the amyloid hypothesis. Imagine a horror movie inside a haunted house with ghosts that gradually intensify in their haunting. Thats the amyloid horrora protein that gradually but silently builds up inside a neuron, the house, eventually stripping it of its normal function and leading to the death of anything inside. Subsequent studies also found other toxic proteins that hang around outside the neuron house that gradually poison the molecular tenants within.

For decades scientists have thought that the best approach to beat these ghosts was an exorcismthat is, to get rid of these toxic proteins. Yet in trial after trial, they failed. The failure rate for Alzheimers treatmentso far, 100 percenthas led some to call treatment efforts a graveyard of dreams.

Its pretty obvious we need new ideas.

A few years ago, two hotshots strolled into town. One is CRISPR, the wunderkind genetic sharpshooter that can snip way, insert, or swap out a gene or two (or more). The other is iPSCs, induced pluripotent stem cells, which are reborn from adult cells through a chemical bath.

The two together can emulate Dementia 2.0 in a dish.

For example, using CRISPR, scientists can easily insert genes related to Alzheimers, or its protection, into an iPSCeither that from a healthy donor, or someone with a high risk of dementia, and observe what happens. A brain cell is like a humming metropolitan area, with proteins and other molecules whizzing around. Adding in a dose of pro-Alzheimers genes, for example, could block up traffic with gunk, leading scientists to figure out how those genes fit into the larger Alzheimers picture. For the movie buffs out there, its like adding into a cell a gene for Godzilla and another for King Kong. You know both could mess things up, but only by watching what happens in a cell can you know for sure.

Individual labs have tried the approach since iPSCs were invented, but theres a problem. Because iPSCs inherit the genetic baseline of a person, it makes it really difficult for scientists in different labs to evaluate whether a gene is causing Alzheimers, or if it was just a fluke because of the donors particular genetic makeup.

The new iNDI plan looks to standardize everything. Using CRISPR, theyll add in more than 100 genes linked to Alzheimers and related dementias into iPSCs from a wide variety of ethnically diverse healthy donors. The result is a huge genome engineering project, leading to an entire library of cloned cells that carry mutations that could lead to Alzheimers.

In other words, rather than studying cells from people with Alzheimers, lets try to give normal, healthy brain cells Alzheimers by injecting them with genes that could contribute to the disorder. If you view genes as software code, then its possible to insert code that potentially drives Alzheimers into those cells through gene editing. Execute the program, and youll be able to observe how the neurons behave.

The project comes in two phases. The first focuses on mass-engineering cells edited with CRISPR. The second is thoroughly analyzing these resulting cells: for example, their genetics, how their genes activate, what sorts of proteins they carry, how those proteins interact, and so on.

By engineering disease-causing mutations in a set of well-characterized, genetically diverse iPSCs, the project is designed to ensure reproducibility of data across laboratories and to explore the effect of natural variation in dementia, said Dr. Bill Skarnes, director of cellular engineering at the Jackson Laboratory, and a leader of the project.

iNDI is the kind of initiative thats only possible with our recent biotech boost. Engineering hundreds of cells related to Alzheimersand to share with scientists globallywas a pipe dream just two decades ago.

To be clear, the project doesnt just generate individual cells. It uses CRISPR to make cell lines, or entire lineages of cells with the Alzheimers gene that can pass on to the next generation. And thats their power: they can be shared with labs around the world, to further hone in on genes that could make the largest impact on the disorder. Phase two of iNDI is even more powerful, in that it digs into the inner workings of these cells to generate a cheat codea sheet of how their genes and proteins behave.

Together, the project does the hard work of building a universe of Alzheimers-related cells, each outfitted with a gene that could make an impact on dementia. These types of integrative analyses are likely to lead to interesting and actionable discoveries that no one approach would be able to learn in isolation, the authors wrote. It provides the best chance at truly understanding Alzheimers and related diseases, and promising treatment possibilities.

Image Credit: Gerd Altmann from Pixabay

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A Massive New Gene Editing Project Is Out to Crush Alzheimer's - Singularity Hub

The human genome has long been a difficult book to read. Modern technological advances have recently opened doors for researchers to begin asking a big question: What parts of our DNA sequences might influence disease? Mary Lauren Benton, Ph.D., recently joined the Baylor Engineering and Computer Science faculty as an assistant professor of bioinformatics, and she is working to answer that question.

Mary Lauren Benton, Ph.D.

If you think of the genome like an instruction manual, Im interested in the grammar, Benton said. Im interested in understanding how short DNA sequences turn genes on and off in different cells and allow for many different outcomes. If we know how a particular sequence influences risk of heart disease, for example, we can use that information to help us guide clinical decisions, whether thats applying different treatments, prescribing different medications or scheduling more preventative care. All of these things can help clinicians to better prioritize and care for patients.

Benton uses computer modeling to look through large data sets of genetic information. Bioinformatics allows for processing of these large data in ways not possible previously, giving room for biological researchers to find patterns and solutions using methods and tools from computer science.

I think of bioinformatics as the intersection of computer science and biology, Benton said. I take tools and methods from computer science, and I apply them to solve fundamental biological questions. We have a lot of really big data sets in biology. The human genome is 3 billion base pairs long, which we cant analyze by hand. The tools from computer science and statistics give us a way to ask questions that we wouldnt be able to otherwise. They open the doors to analyses that would have been impossible even 10 or 20 years ago.

Benton most recently authored The Influence of Evolutionary History on Human Health and Disease, which was published in the Nature Reviews Genetic Journal and takes a look at the evolutionary origins of disease. Being diagnosed with a disease or health problem may feel like a present problem; however, Benton explained that looking at the foundations of a disease is important to understanding how to move forward with treatment.

The foundations and the systems that are involved in disease have really deep evolutionary origins, she said. Cancer might be something that youre diagnosed with today, but the foundation of cancer can be traced back to the idea that we have cells that are able to grow and divide, which also provides the opportunity for tumors to grow.

Benton explained that its important to consider the history of the disease and the systems involved alongside any variants or environmental factors that help to cause the disease. A holistic understanding of disease can influence how patients are treated as well as provide information about how their diseases came to be.

Its not enough to understand whats happening in a person right now or in the last five years, Benton said. Understanding the million-year history of how people got here is equally important to make advances in personalizing medicine, especially genomic medicine. Having that long lens is something that is often lost in the day-to-day operations of a doctors office.

Benton is excited to be evaluating the way that researchers think about decoding genetic information. While a common approach is to think of genes as being able to be turned off or on with a simple switch, that may not be the most accurate approach.

We study these sets of genetic switches and how they turn genes on and off at the right times. Often, we think about these switches working one-at-a-time; the gene is either on or its off, Benton said. But it is much more complicated than that. There are often multiple switches that act more like a dashboard of knobs and dials that all work together to properly tune the output of the genome.

Bentons research is moving toward the development of new models and ways of thinking about how known individual elements are combined and factored into this much larger, more accurate dashboard. Differences based on demographic histories, environmental variables and evolutionary processes all influence the risk of disease in different ways. A better understanding of genomes and how genetic variants relate to disease has major implications for precision medicine.

Its really vital for precision medicine to take into account the full diversity of the human experience. We cant focus on one particular kind of person or one population. People of European ancestry are over-represented in genetic studies, Benton said. Improving diversity and representation in our genomic studies is vital to understanding how the genome relates to disease and to learning how to appropriately treat all of the patients that might walk through the doors of a clinic.

Precision medicine, in some ways, seems futuristic and far-off. But, in other ways, precision medicine is already being used to protect at-risk individuals from diseases like cancer. While widespread precision medicine may not be seen for a long time, research like Bentons plays a role in better understanding disease risk broadly and providing context for clinical solutions moving forward.

Precision medicine is both happening right now and is something that well probably always be working toward, Benton said. There are things that we understand right now about specific genetic variants that might predispose you to a certain kind of breast cancer, for example. We already have diseases that we can test for or treat differently based on someones genotype. But, because the genome is such a complicated thing, walking into the clinic and handing your DNA sequence to the doctor, who would then read it and prescribe the right treatments on the spot, is a goal that well always be working toward. Still, I expect well see big changes in the next five to 10 years given the current rate of progress.

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Grammar of the Genome: Reading the Influence of DNA on Disease - Baylor University

The information and biotechnology revolutions have changed our world and will heavily inform the future of society. Whoever controls these technologies controls the future, and whoever controls their standardization controls the technologies. China understands this well. For two decades, it has been working to take over international standardization rulemaking bodies to serve the goals advanced in Made in China 2025 that is, to dominate world manufacturing and then transition to become the center of the worlds technological innovation

The dangers to the United States are already present, and in forms that are not obvious. These include, first, direct-to-consumer genetic testing. China may be using such testing to gain genetic information that permits the identification and tracking of Americans, including U.S. military and intelligence community personnel or their relatives. Second, health monitoring apps are able to provide geolocation data to Chinese entities, which means to the Chinese Communist Party (CCP) and its security services. This provides location data that is valuable on its own and might be compared with data from other sources to reveal key information about Americans. Third, the CCP, in cooperation with Chinese industrial entities on international bodies, are developing and setting international standards for emerging technologies. Chinas influence has grown over the past two decades, and Beijing now possesses leadership roles in standards-drafting technical committees, which means it could shape outcomes to its benefit.

China has formulated a four-step strategy to seek dominance in this area: plan, track, participate and take over. Beijing has boasted that it completed the first three steps and is on the last, which is to develop indigenous standards and to lead international standardization. This means China may be replacing international standards with its own standards, in order to control technologies and the market. In 2017, China revised its standardization law, almost 30 years after its adoption in 1989. It also set up the Standardization Administration of China to implement its strategy in the early 2000s. Chinas standardization strategy also has been incorporated into the Belt and Road Initiative so that, as countries are weaved into this network, they adopt Chinas standards.

Beijing essentially has had the three primary standard-setting international organizations the International Organization for Standardization (ISO), the International Telecommunication Union (ITU) and the International Electrotechnical Commission (IEC) under its influence. Two Chinese government officials currently serve as president of ITU and IEC, and placed Chinas proxy as the head of the ISO after the organization was led by a Chinese official for many years. Meanwhile, Beijing has taken leadership or other influential positions in the International Accreditation Forum (IAF), United Nations Industrial Development Organization (UNIDO), International Civil Aviation Organization (ICAO), American Society for Quality (ASQ) and perhaps others.

Chinas strategy to determine the worlds standards appears to be working. In 2019 alone, China submitted 830 standards proposals to the ITU. According to Zhang Xiaogang, former president of the ISO, China planned to initiate 395 international standards by 2020 but, in actuality, it set 495. Zhang claims that China has made the greatest contribution in the field of international standardization in the past five years. Indeed, China has dominated 5G standard-setting, for example, in the 3rd Generation Partnership Project (3GPP), an organization to develop mobile broadband standards, and 90 percent of standard proposals in the 5G super uplink field is done by China Telecom.

Unfortunately, Western countries fail to see the importance of Chinas strategic move. Zhang states, Whoever leads in standard-setting will be the leader of the technology and the controller of the market. Chinas dominance in 5G standards-setting enables it to avoid the Wests sanctions against its tech giants such as Huawei, continue to expand globally, and to dominate the market. This could be a paramount communication-security problem for the U.S.

Of particular importance is Chinas standardization strategy as identified in China Standards 2035 on international bodies engaged in developing and setting standards for select emerging technologies. These include advanced communication technologies and cloud computing and cloud services. The United States and its allies must ensure that international standards for emerging technologies are not being designed to promote the interests of China. If China is successful, it would lead to the exclusion of other participants; China would be the architect, builder and maintainer of the 21st centurys information technology infrastructure.

Washington must take steps to bolster U.S. public- and private-sector participation in international standards-setting bodies. The U.S. must underscore the dangers of interacting with Chinese firms. The government, particularly the Department of Homeland Security, has called attention to this, but there is little recognition that U.S. firms understand the risks associated. There must be greater awareness of smartphone apps, which should be graded on user privacy and their security from Chinese penetration. And U.S. entities that permit Chinese entities to exploit data should be subject to possible legal action.

A key question of the 21st century is a holdover from the previous century: Which state will control scientific knowledge and its standards? The answer is not yet clear. Thankfully, in the 20th century, the U.S. surpassed Nazi Germany to dominate physics and related sciences and industries, and generated the centurys most fearsome weapon the atomic bomb and its progeny, the hydrogen bomb.

If these revolutionary advances occur within the framework of the U.S.-led liberal international order, we are assured improvements to the well-being of people. But if China leads the scientific and technological revolution, these advances will serve the CCPs inherently malign interests. China will aggressively seize opportunities, particularly in nascent areas where standards are not developed including biotechnology, genetic engineering, energy production and distribution technologies, aerospace, 5G and artificial intelligence.

If China has its way in standards-setting, the communist regime will control these critical technologies and the global supply chain. That means it would dominate the future of the free worlds economy, media and politics. The United States no longer can afford complacency.

Bradley A. Thayer is the co-author of How China Sees the World: Han-Centrism and the Balance of Power in International Politics.

Lianchao Han is vice president of Citizen Power Initiatives for China. After the Tiananmen Square massacre in 1989, he was one of the founders of the Independent Federation of Chinese Students and Scholars. He worked in the U.S. Senate for 12 years, as legislative counsel and policy director for three senators.

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We cannot let China set the standards for 21st century technologies | TheHill - The Hill

This spring, the biotechnology company Oxitec plans to release genetically modified (GM) mosquitoes in the Florida Keys. Oxitec says its technology will combat dengue fever, a potentially life-threatening disease, and other mosquito-borne virusessuch as Zika mainly transmitted by the Aedes aegypti mosquito.

While there have been more than 7,300 dengue cases reported in the United States between 2010 and 2020, a majority are contracted in Asia and the Caribbean, according to the U.S. Centers for Disease Control and Prevention. In Florida, however, there were 41 travel-related cases in 2020, compared with 71 cases that were transmitted locally.

Native mosquitoes in Florida are increasingly resistant to the most common form of control insecticideand scientists say they need new and better techniques to control the insects and the diseases they carry. There arent any other tools that we have. Mosquito nets dont work. Vaccines are under development but need to be fully efficacious, says Michael Bonsall, a mathematical biologist at the University of Oxford, who is not affiliated with Oxitec but has collaborated with the company in the past, and who worked with the World Health Organization to produce a GM mosquito-testing framework.

Bonsall and other scientists think a combination of approaches is essential to reducing the burden of diseasesand that, maybe, newer ideas like GM mosquitoes should be added to the mix. Oxitecs mosquitoes, for instance, are genetically altered to pass what the company calls self-limiting genes to their offspring; when released GM males breed with wild female mosquitoes, the resulting generation does not survive into adulthood, reducing the overall population.

But Oxitec has been proposing to experimentally release GM mosquitos in the Keys since 2011, and the plan has long been met with suspicion among locals and debate among scientists. Some locals say they fear being guinea pigs. Critics say they are concerned about the possible effects GM mosquitoes could have on human health and the environment. In 2012, the Key West City Commissionobjected to Oxitecs plan; in a non-binding referendum four years later, residents of Key Havenwhere the mosquitoes would have been releasedrejected it, while residents in the surrounding county voted in support of the release. With the decision left up to the Florida Keys Mosquito Control District, officials approved the trial to be conducted elsewhere in the Keys.

According to Oxitec, the release was delayed due to a transfer of jurisdiction over the project from the U.S. Food and Drug Administration to the Environmental Protection Agency.

The company reapplied for approval to release a new version of the mosquitoes, called OX5034, in the Keys. In May, the EPA granted a two-year experimental use permit, which the agency can cancel at any time. State and local sign-off soon followedfinally giving the project the greenlight.

Oxitecs OX5034 mosquitoes are the first GM mosquitoes approved for release in the US. The company has already conducted a trial with the OX5034 mosquitoes in Brazil and released more than a billion of a previous version, called OX513A, there and in other locations over the yearsincluding the Cayman Islands. The company says it is confident in the effectiveness and safety of the technology.

But some scientists want to hit pause on Oxitecs Florida trial, to find what they say is a fairer process in deciding to release the mosquitoes. Others want to see clearer proof that this technology is even necessary, claiming that the company has only released its most positive data with the public and has kept other key data, including whether the mosquitoes curb disease transmission, private. And if the release actually launches as planned, some Keys residents say they aim to interfere.

Critics also say that Oxitec failed to engage with local communities in Florida and get their consent to release the mosquitoes. Whats the most upsetting is that the very people that are going to be most impacted, both by the benefits or the risks of such a decision, have like the smallest voice in how these choices are made. I think thats a really big issue, says Natalie Kofler, a molecular biologist and bioethicist who founded Editing Nature, a platform that advocates for inclusive decision-making processes to steer the use of genetic technology. If Oxitec doesnt do this right, she adds, we could have huge impact on delaying the use of other beneficial technologies like that in the future.

Oxitecs OX5034 mosquitoes are programmed to combat the transmission of mosquito-borne illnesses by suppressing local Aedes aegypti populations. Oxitecwhich is US-owned and based in the United Kingdomdescribes their mosquitoes as friendly because they will only release males, which, unlike females, do not bite humans or transmit disease.

At Oxitecs laboratory in the UK, the company genetically engineers the mosquitoes, giving the insects the self-limiting gene that makes the females dependent on the antibiotic tetracycline. Without the drug, they will die. Eggs from these genetically-altered mosquitoeswhich will hatch both male and female insectswill be shipped to the Keys. Mosquitoes require water to mature from an egg to an adult; when Oxitecs team adds water to the boxes the mosquitoes will be deployed in, both GM males and GM females will hatch. With no tetracycline present in the box, the GM females are expected to die in early larval stages.

The male mosquitoes will survive and carry the gene. When they leave the boxes, the insects will, hypothetically, fly away to mate with wild females to pass the gene to the next wild generation, according to Nathan Rose, head of regulatory affairs at Oxitec. Kevin Gorman, the companys chief development officer, says the local female mosquito population will be increasingly reducedwhich will also reduce the number of wild male mosquitoes in the treatment areas.

Gorman emphasized to Undark that the EPA and other regulators found no risk in using tetracycline in breeding their genetically-altered mosquitoes. But some scientists think the presence of this antibiotic in the environment does pose a risk. According to Jennifer Kuzma, co-founder and co-director of the Genetic Engineering and Society Center at North Carolina State University, tetracyline is commonly used in Florida to prevent bacterial diseases in agricultureparticularly in citrus grovesand to treat bacteria in sewage plants. The use of the antibiotic for these purposes may mean that it will remain in the environment, especially in water where the mosquitoes breed, which could allow Oxitecs female mosquitoes to survive. While the company does not plan to release the mosquitos near areas where the antibiotic is used, Kuzma says the EPAs risk assessment did not include testing of any standing water for tetracyclinesomething, she adds, would have been easy enough to do for good due diligence.

Skeptics of Oxitecs GM mosquitoes include local residents, physicians, scientists, and environmental activists. Many of these opponents say they arent anti-GMO, but disagree with how the approval process has been handled. One group has even kept a running list of what it sees as Oxitecs wrongdoings since it first began experimental releases. The list includes Oxitecs lack of disease monitoring in the countries where it has released mosquitoes; the unknown price of its technology; and complaints that the company has overstated the success of some of it its trials.

I cannot trust this company. I cannot trust this technology, says Mara Daly, a resident of Key Largo who says shes been following Oxitecs plans for nine years.

This is not a traditional pesticide, she adds. This is not a chemical that you can trace. This is something completely different, new emerging technology and we need better regulation.

Phil Goodman, chairman of the Florida Keys Mosquito Control District (FKMCD), an independently-elected commission carrying out mosquito control within Monroe County, says that many of those who discredit Oxitecs evidence do not understand the technology. Theyre fearmongering, he says.

They have very little credibility here in the Florida Keys as far as Im concerned, he adds.

But people like Daly and Barry Wray, executive director of the Florida Keys Environmental Coalition, disagree. We want to know its safe, says Wray, who notes that his group more generally supports GM technology. We dont have another Florida Keys ecosystem. We dont have another Florida Keys community. We have this one.

Daly, Wray, and others point to what they perceive as the FKMCDs disrespect for public opinion. They argue that the community wasnt given a chance to consent before the EPA approval. There was a 30-day public forum in September 2019 about Oxitecs technology application, with 31,174 comments opposing release and 56 in support. A statement emailed to Undark by Melissa Sullivan, an EPA spokesperson, noted that the agency considered these comments during the review, but critics think it happened too quickly to be of real use.

In June, Kofler and Kuzma wrote an opinion piece in The Boston Globe about the EPA approval, critiquing the agencys regulatory system and calling for a better process for evaluating new biotechnologies. The researchers expressed concern that the EPA did not convene an independent, external scientific advisory panel to review Oxitecs claims about its mosquito strategy and that the agency only publicly released its risk assessment after approving the technology. The American public, Kofler and Kuzma wrote, needs to be assured that these decisions are made free of conflicts of interest. The statement from the EPAs Sullivan noted that the agency conducted anextensive risk assessmentbased on the best available science.

Some critics also wanted there to be more public engagement. Kofler and Kuzma say they offered to provide their expertise, along with other outside experts, to the mosquito control district to allow more discussion about the GM mosquitoes with the Keys community. But Kofler says the district wasnt responsive. Oxitec itself launched webinars about their new product, but not until after the EPA approval. Here we are, like in the final hour, having these conversations that needed to be happening a year ago, says Kofler.

Without public trust and enthusiasm, it doesnt matter whether Oxitecs mosquito technique works, says Guy Reeves, a genetic researcher at the Max Planck Institute for Evolutionary Biology in Germany, who stresses that he doesnt think the companys approach is unsafe. If the population in Florida Keys becomes so sensitized to this issuethat they can no longer cooperate with each otherthats good for the mosquitoes, not good for the people, he adds.

Based on their first generation mosquito OX513A, Oxitec says it has shown that the approach reduces a targeted mosquito population in trials in both Brazil and the Cayman Islands. But theres no evidence that this new OX5034 mosquito release will actually be worth it for mosquito suppression, says Reeves. Oxitec also hasnt explained how their new mosquito will directly curb human diseases, such as dengue. Reducing disease transmission and burden should be measures of efficacy for this technology, says Kofler.

According to Gorman, independent disease suppression data has only been collected by municipalities in Brazil because thats where most of the companys trials have been released in larger scales. These municipalities have shown that Oxitec mosquitoes have reduced dengue cases in areas of release, Gorman says. In order for Oxitec to collect additional data, he adds, the company needs to release and test large areas over sustained periods of time. Gorman maintains that the company is not required to report formal health impact studies.

Reeves adds that Oxitec also hasnt explained what resources are needed to sustain this product, how long it could take to be effective, or the cost. When asked about the cost of the Florida Keys project, Oxitec responded to Undark by email: Oxitec is a pre-commercial, pre-profit company. We will not profit from this pilot project in Florida.We are paying for it ourselves.

Oxitec has released more than a billion of their OX513A mosquitoes over the past 10 years. According to independent scientists, some of those experiments did not go well.

For example, researchers at Yale University and collaborators from Brazil analyzed Oxitecs 2015 release of OX513A in Brazil. The scientists confirmed that some offspring of the genetically modified mosquitoeswhich were supposed to die and not pass new genes to the wild populationsurvived to adulthood and mated with their native counterparts. Between 10 and 60 percent of the native mosquitoes contained genes from Oxitec, according to the Yale study, which published in Nature in 2019. The papers authors concluded they do not know what impacts these mixed mosquitoes have on disease control or transmission, but added that their findings underscore the importance of monitoring the genetics of the insects.

Oxitec disagreed with the findings and responded on the journals website. Oxitec told Gizmodo that Yales study includes numerous false, speculative, and unsubstantiated claims and statements about Oxitecs mosquito technology. And when Kofler and three other scientists wrote about Oxitecs Brazil trial in The Conversation, Oxitec pushed to have the article retracted, says Kofler.

For this coming release, some Key Largo locals are willing to act on their anger. Daly, for instance, says that if the mosquitoes are deployed in her neighborhood, shell try to put insecticide in any box she finds or send it to an expert to testeven if it means getting in trouble with the federal authorities. I already have my arresting officer and she said shes gonna clean her handcuffs for me, she says. I dont care.

Ideally, Daly says, it wont have to come to that. She and other locals hope to stop Oxitec before the latest mosquitos are delivered. Daly says she has been busy organizing protests like one that happened recently in Key Largoand giving out yard signs to residents who dont want their property used in the trial. Locals are pissed off. So I have been busy getting the press to cover the local opposition, Daly wrote in an email to Undark.

The first flying insect or animal that can actually use our human blood for a friggin trial for a product to come to market without my consent, Daly says.

Thats my blood, she adds. Thats my sons blood. Thats my dogs blood.

This article was originally published on Undark. Read the original article.

Image Credit: Frauke Feind from Pixabay

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First GMO Mosquitoes to Be Released in the Florida Keys - Singularity Hub

GAITHERSBURG, Md., April 14, 2021 /PRNewswire/ -- Novavax, Inc. (Nasdaq: NVAX), a biotechnology company developing next-generation vaccines for serious infectious diseases, today announced its participation in a newly expanded investigator-initiated Phase 2 clinical trial called Comparing COVID-19 Vaccine Schedule Combinations Stage 2(Com-COV2), to be conducted by the University of Oxford and supported by the UK Vaccines Taskforce. Novavax' recombinant protein vaccine candidate, NVX-CoV2373, is one of four COVID-19 vaccines that will be studied to evaluate the potential for combined regimens that mix vaccines from different manufacturers to achieve immune protection against COVID-19.

"Novavax' addition to this important study reflects the urgency of finding innovative ways to protect as many people as possible in a dynamic pandemic landscape," said Filip Dubovsky, M.D., Executive Vice President, Chief Medical Officer, Novavax. "The potential utility of pooling public health resources, including all available vaccines, could help us get ahead of an evolving virus."

Com-COV2 will include 1050 adults 50 years of age or older who received their first vaccination during the prior 8-12 weeks. Volunteer study participants will receive one of four different vaccines as a second dose, 350 of whom will be administered NVX-CoV2373. The research will compare the immune system responses from those who receive a heterologous regimen to those who receive a homologous regimen.

"The focus of these studies is to explore whether multiple COVID-19 vaccines can be used more flexibly, with different vaccines being used for the first and second doses," said Matthew Snape, Associate Professor in Paediatrics and Vaccinology at the University of Oxford, and Chief Investigator on the trial. "If we can show that these mixed schedules generate an immune response that is as good as the standard schedules, this could potentially allow more people to complete their COVID-19 immunization course more rapidly."

Under the protocol, which is a designed as a non-inferiority study, participants will be followed for reactogenicity (safety) and immune responses. The UK Medicines and Healthcare products Regulatory Agency (MHRA) and Joint Committee on Vaccination and Immunisation (JCVI) will formally assess the safety and efficacy of any new vaccination regimen before it is made available to the public.

About NVX-CoV2373NVX-CoV2373 is a protein-based vaccine candidate engineered from the genetic sequence of SARS-CoV-2, the virus that causes COVID-19 disease. NVX-CoV2373 was created using Novavax' recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and is adjuvanted with Novavax' patented saponin-based Matrix-M to enhance the immune response and stimulate high levels of neutralizing antibodies. NVX-CoV2373 contains purified protein antigen and can neither replicate, nor can it cause COVID-19. In preclinical studies, NVX-CoV2373 induced antibodies that blocked the binding of spike protein to cellular receptors and provided protection from infection and disease. It was generally well-tolerated and elicited robust antibody response in Phase 1/2 clinical testing.

NVX-CoV2373 is being evaluated in two pivotal Phase 3 trials, a trial in the U.K that demonstrated efficacy of 96.4% against the original virus strain and 89.7% overall, and the PREVENT-19 trial in the U.S. and Mexico that began in December 2020. It is also being tested in two ongoing Phase 2 studies that began in August 2020: A Phase 2b trial in South Africa that demonstrated 48.6% efficacy against a newly emerging escape variant, and a Phase 1/2 continuation in the U.S. and Australia.

NVX-CoV2373 is stored and stable at 2- 8C, allowing the use of existing vaccine supply chain channels for its distribution. It is packaged in a ready-to-use liquid formulation in 10-dose vials.

About Matrix-MNovavax' patented saponin-based Matrix-M adjuvant has demonstrated a potent and well-tolerated effect by stimulating the entry of antigen presenting cells into the injection site and enhancing antigen presentation in local lymph nodes, boosting immune response.

About NovavaxNovavax, Inc.(Nasdaq: NVAX) is a biotechnology company that promotes improved health globally through the discovery, development and commercialization of innovative vaccines to prevent serious infectious diseases. The company's proprietary recombinant technology platform combines the power and speed of genetic engineering to efficiently produce highly immunogenic nanoparticles designed to address urgent global health needs. Novavaxis conducting late-stage clinical trials for NVX-CoV2373, its vaccine candidate against SARS-CoV-2, the virus that causes COVID-19. NanoFlu, its quadrivalent influenza nanoparticle vaccine, met all primary objectives in its pivotal Phase 3 clinical trial in older adults and will be advanced for regulatory submission. Both vaccine candidates incorporate Novavax' proprietary saponin-based Matrix-M adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies.

For more information, visit http://www.novavax.com and connect with us on Twitter and LinkedIn.

Novavax Forward Looking StatementsStatements herein relating to the future of Novavax and the ongoing development of its vaccine and adjuvant products are forward-looking statements. Novavax cautions that these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include those identified under the heading "Risk Factors" in the Novavax Annual Report on Form 10-K for the year ended December 31, 2020, as filed with the Securities and Exchange Commission (SEC). We caution investors not to place considerable reliance on forward-looking statements contained in this press release. You are encouraged to read our filings with the SEC, available at sec.gov, for a discussion of these and other risks and uncertainties. The forward-looking statements in this press release speak only as of the date of this document, and we undertake no obligation to update or revise any of the statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties.

Contacts:

InvestorsNovavax, Inc.Erika Schultz | 240-268-2022ir@novavax.com

Solebury TroutJennifer Porcelli | 646-378-2962jporcelli@soleburytrout.com

Novavax MediaAmy Speak | 617-420-2461Laura Keenan | 410-419-5755media@novavax.com

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Novavax to Participate in University of Oxford Com-COV2 Study Comparing Mixed COVID-19 Vaccine Combinations - BioSpace

Washington State-based AmunBio and Chicago-based NorthShore University HealthSystems Research Institute have agreed to collaborate in the development and the commercialization of an innovative technology platform of novel immunotherapeutic oncolytic viruses. AmunBio has an exclusive option to license this technology.

The proprietary platform technology has the potential to generate a strong pipeline of patient-centric next-generation immunotherapeutic oncolytic viruses.

The conceptOncolytic viruses are a form of immunotherapy that uses native or reprogrammed viruses to infect and selectively kill cancerous cells. The concept of using viruses in killing cancer is, however, not new. At the turn of the nineteenth century, when the existence of viruses was first recognized, there has been considerable interest in using viruses as possible agents of tumor destruction.

The use of viruses in cancer treatment was not the result of true understanding and discerning theory of a possible therapy, but rather, was based on the observation that, in some cases, patients diagnosed with cancer or hematological malignancies who contracted an infectious disease went into brief periods of clinical remission

Early case reports emphasized regression of cancers during naturally acquired virus infections, providing the initial basis for clinical trials where body fluids containing human or animal viruses were used to transmit infections to cancer patients.

In one case, in a patient diagnosed with leukemia, it was well recognized that the contraction of influenza produced beneficial effects. And while doctors were not able to report cases where an accompanying infectious disease led to a complete cure of leukemia, they believed that a treatment based upon the causal infection would, potentially, provide an alternative to the hopelessness of the ordinary treatment of leukemia.'[1]

And while in this approach of infecting cancer patients the immune system arrested the impact of the viruses in most cases, and the viruses failed to impact tumor growth, when, in immunosuppressed patients, infection persisted, tumors regressed. However, morbidity as a result of the infection of normal tissues was unacceptably high, ending attempts to develop novel virus-based treatment options.[2]

In the 1950s and 1960s, with the advent of rodent models and new methods for virus propagation, researchers attempted to develop viruses with greater tumor specificity, but success was limited, and, again, most researchers abandoned their research in finding a virus to kill cancer in the 1970s and 1980s. [2]

ResurgenceHowever, more recently, there has been a resurgence of interest in finding viruses that can be used to target and attack tumors that have already formed. Some of these modifiied virusesbut not allare known as oncolytic viruses and represent a promising approach to treating cancer. And today, the development of oncolytic viral therapies, which represents a unique therapeutic paradigm within Immuno-Oncology, is rapidly gaining momentum.

In November 2005 research and development of oncolytic viruses got a welcome boost when Chinese medical regulators approved Shanghai Sunway Biotechs genetically modified adenovirus oncorine (H101). This drug was the worlds first oncolytic viral therapy for the treatment of nasopharyngeal carcinoma in combination with chemotherapy after the phase III clinical trial. At the same time, the company also bought the rights to Onyx-15 (dl1520), an almost identical oncolytic virus* developed by Onyx Pharmaceuticals which was scheduled to be included into phase III clinical trials for lung cancer in 2000.

Onyx-15The development of Onyx-15 began in 1996 when Frank McCormick***, Ph.D. FRS, the co-founder of Onyx Pharmaceuticals and one of the companys biochemists, initiated and led various drug discovery efforts.

McCormick believed that an adenovirus without its E1B gene, which inactivates the host cells p53 gene, would be able to selectively kill cancer cells. He believed that because normal cells harboring the modified virus, the defenseless virus would be subject to p53-mediated cell cycle arrest, preventing the virus from replicating. Cancer cells lacking p53 would be thus be unable to halt viral replication and would be lysed, with multiplied viruses bursting out to infect and destroy the entire tumor.

Unfortunately, while McCormicks hypothesis seemed brilliant, it was also incorrect. Research shoeed that Onyx-15 was not specific for p53-null cells. However, in early human trials, the oncolytic virus still killed tumor cells preferentially and was superior to chemotherapy alone. In its phase III trial with oncorine, Shanghai Sunway Biotech reported a 79% response rate for oncorine plus chemotherapy, compared with 40% for chemotherapy alone.

While various key opinion leaders and experts believe that a completed phase III trial of Onyx-15 would have resulted in FDA approval, the development and phase III clinical trial of the oncolytic virus was suspended when Pfizer acquired Warner-Lambert, Onyxs development partner.

Looking back, if approved, Onyx-15 would, as some experts suggest, been made obsolete by better oncolytic viruses. One of the reasons is that the deletion of E3 limited the potency of Onyx-15. But the suspension of the phase III trial stigmatized the development of oncolytic viruses because, as a result, many researchers inaccurately assumed that Onyx-15 trial failed. In reality, the trial never started.

MelanomaIn 2015, the U.S. Food and Drug Administration (FDA) approved the first oncolytic virus immunotherapy for the treatment of cancer called talimogene laherparepvec or T-VEC (Imlygic; Amgen). The treatment is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. Talimogene laherparepvec involves a herpes virus that has been engineered to be less likely to infect healthy cells as well as cause infected cancer cells to produce the immune-stimulating GM-CSF protein.

While in clinical trials and following regulatory approval oncolytic viruses have indeed met the challenge and have become a valuable tool in the anti-cancer armamentarium, there is still much work that needs to be done in the development of novel immunotherapeutic agents based on this approach.

AgreementThe Research Institute has granted an exclusive option to AmunBio covering intellectual property and technology related to an immunotherapeutic oncolytic virus platform. This technology forms the core of AmunBios proprietary, multimodal therapeutic approach utilizing direct destruction of cancer cells and immune system activation.

The technology is based on more than 20 years of research by Prem Seth, Ph.D., Director, Gene Therapy Program at NorthShore, and AmunBios founder and Chief Scientific Officer, and his associates.

AMUN-003The agreement between AmunBio and NorthShore University HealthSystems Research Instituteincludes the development of AMUN-003, an adenovirus-based immunotherapeutic Immuno-Oncology agent, which is being developed for the treatment of multiple solid tumors, including (triple-negative) breast cancer (TNBC) and melanoma, and the ongoing development of additional immunotherapeutic oncolytic viruses.

Following a planned Investigational New Drug (IND) application, which is expected in late 2021/early 2022, AmunBio is planning multiple Phase I clinical trials of AMUN-003 alone or in combination with checkpoint inhibitors.

AmunBios AMUN-003 blocks suppression of the immune response inside the tumor stimulates the recruitment of cancer-killing immune cells and avoids non-specific inflammation. AMUN-003 can be administered both locally as well as systemically.Preclinical studies with AMUN-003 in breast cancer alone, compared to prior oncolytic virus constructs, demonstrated near-complete breast cancer inhibition. [3]

Based on preclinical studies, we believe that AMUN-003 may lead to long-term protection from cancer recurrence, Seth said.

Incidence of cancerWe believe that in the treatment of cancer, there are still not enough new options, noted Cecilia Zapata-Harms, MS, MHA, AmunBio Chief Operations Officer.

While last year, in 2020, the world focused on the SARS-CoV-2 pandemic, more than 9 million people worldwide lost their fight against cancer. *** [4] Among them were more than 600,000 Americans. Our novel viral immunotherapeutic approach may result in significantly more efficacious treatment options, promising to dramatically improve the outcome for many patients diagnosed with cancer, she observed.

We are delighted to be partnering with NorthShore and to be part of ongoing research initiatives to improve the lives of patients, said Zapata-Harms, commenting on research collaboration with the Research Institute.

Breakthrough researchThe Research Institute is the research arm of NorthShore University and supports the organizations core mission to preserve and improve human life through academic excellence and innovative research. The scientists at the research are involved in a wide range of research activities, from lab-based translational research and advanced imaging to clinical trials. As part of this, NorthShore providing the infrastructure and resources for research, which include both administrative and regulatory oversight of investigative studies. The organization has a long history of firsts.

Were humbled by the fact that the same institution, where in the early 1920s George Frederick Dick, MD, and Gladys Henry Dick, MD pioneered the development of a toxin for the prevention of scarlet fever, stands behind our work in developing engineered oncolytic virus for Immuno-Oncology. Its also the same institution where the American pediatrician Louis Wendlin Sauer, MD, in the 1930s, perfected a vaccine used to prevent pertussis (whooping cough), and, more recently, scientists have developed novel treatment options for diseases like MRSA, reducing infection rates through the study of preventative screenings and diagnostic testing, said Andrei R. Shustov, MD, a member of AmunBio Scientific Advisory Board.[5][6]

Oncolytic viruses represent a unique therapeutic approach within Immuno-Oncology and AmunBio platform technology is expected to result in a fundamental shift, augmenting novel treatment modalities compared to, what we believe, is possible today, said, Stephen R. Wachtel, Ph.D., Assistant Vice President, Research Operations at NorthShore.

With the collaboration between the Research Institute and AmunBio were able to address many of the challenges that have prevented previous endeavors from delivering on the full potential of immunotherapeutic oncolytic viruses within Immuno-Oncology, allowing us to discover and develop novel drug candidates for some of the most challenging cancers, Wachtel concluded.

Note*The only difference between the two oncolytic viruses is a slightly larger deletion in H101s E3 gene, which affects immune response**Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Around the world, much work is being done to develop new treatment options.***Today Frank McCormick, Ph.D. FRS, professor in the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center

Clinical trialsSystemic Chemotherapy Combined With Recombinant Human Adenovirus Type 5 and Endostatin Injections for Treatment Malignant Hydrothorax in NSCLC Patients NCT02579564Intraperitoneal Injection of Oncolytic Viruses H101 for Patients With Refractory Malignant Ascites NCT04771676

Highlights of prescribing informationTalimogene laherparepvec (Imlygic; Amgen, Inc) [Prescribing Information]

Reference[1] Kelly E, Russell SJ. History of oncolytic viruses: genesis to genetic engineering. Mol Ther. 2007 Apr;15(4):651-9. doi: 10.1038/sj.mt.6300108. Epub 2007 Feb 13. PMID: 17299401.[2] Data on file AmunBio[3] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021 Feb 4. doi: 10.3322/caac.21660. Epub ahead of print. PMID: 33538338.[4] Dick GF, Dick GH. Scarlet Fever. Edinb Med J. 1934 Jan;41(1):1-13. PMID: 29645766; PMCID: PMC5314226.[5] Pittman M. History of the development of pertussis vaccine. Dev Biol Stand. 1991;73:13-29. PMID: 1778306.

Featured image: A microscopic view of a virus with a depth of field. Photo courtesy: 2020 2021 AmunBio, Inc. Used with permission

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AmunBio and NorthShore University to Advance Cancer Immunotherapy with Engineered Oncolytic Viruses - OncoZine

RESEARCH TRIANGLE PARK, N.C.--(BUSINESS WIRE)-- StrideBio, Inc., a leading developer of novel adeno-associated viral (AAV)-based gene therapies, today announced the signing of a multi-technology collaboration with Duke University that will enable novel next-generation gene therapies against a broad range of disorders. StrideBio is advancing multiple products incorporating these technologies with an initial program targeting a novel treatment for the pediatric neurological disorder Alternating Hemiplegia of Childhood (AHC).

The agreements announced today provide StrideBio an exclusive license to multiple technologies that will enable best-in-class next-generation gene therapies developed at Duke University. Included are novel engineered AAV vectors which complement StrideBios existing STRIVETM capsid engineering platform, having been selected through a cross-species evolution that results in significantly enhanced tropism and potency versus AAV9 across a wide range of tissues such as CNS, skeletal and cardiac muscle. Data on these novel vectors were presented by Duke researcher and StrideBio co-founder, Aravind Asokan, Ph.D., at the American Society of Gene & Cell Therapy 23rd Annual Meeting in an abstract titled Cross Species Evolution of Synthetic AAV Strains for Clinical Translation (Gonzalez et al., ASGCT 2020, Abstract 24). In addition, StrideBio has licensed exclusive rights covering a novel use of IgG-degrading enzyme IdeZ to clear neutralizing antibodies in conjunction with AAV gene therapy administration. This innovative approach was recently published by members of the Asokan Lab in a manuscript titled Rescuing AAV gene transfer from neutralizing antibodies with an IgG-degrading enzyme (Elmore et al., JCI Insight, 2020, 5(19): e139881). Finally, StrideBio obtained license rights to a novel gene therapy approach for the treatment of AHC recently published by Duke researcher Mohamad Mikati, M.D., in a manuscript titled AAV Mediated Gene Therapy in the Mashlool, Atp1a3Mashl/+, Mouse Model of Alternating Hemiplegia of Childhood (Hunanyan et al., Human Gene Therapy, February 12, 2021).

Under the Master Sponsored Research Agreement (SRA), StrideBio will fund collaborative work to advance novel gene therapies initially against AHC and other undisclosed targets. AHC is a devastating pediatric neurological disorder with mutations in a causative gene, ATP1A3, that was first identified by a team of Duke University researchers, including Dr. Mikati, in 2012. StrideBio will work closely with Dr. Mikati using a mouse model of AHC developed in his lab to select and rapidly advance a novel gene therapy candidate to the clinic, leveraging the engineered AAV vectors developed by StrideBio along with its manufacturing and translational development capabilities.

The Master SRA between StrideBio and Duke University also provides a framework for additional new programs to be brought under the collaboration. These programs will aim to utilize novel engineered AAV capsids developed by StrideBio to improve potency, evade neutralizing antibodies and enhance specific tropism to tissues of interest. One additional undisclosed program targeting the CNS vasculature has been initiated.

We are very excited to partner with Duke University to advance these technologies that can improve and expand on the potential benefits of gene therapies for patients who desperately need them, stated Sapan Shah, Ph.D., Chief Executive Officer, StrideBio, Inc. We look forward to working together with a fantastic group of Duke researchers and clinicians to bring next-generation AAV-based gene therapies to patients with rare CNS diseases and beyond, starting with Alternating Hemiplegia of Childhood.

This License and Master Sponsored Research Agreement will ensure that these innovative technologies receive the resources and expertise necessary to develop treatments that can ultimately benefit patients. We are delighted to have StrideBio as a partner on this important effort in the gene therapy area, commented Robin Rasor, Executive Director of the Office of Licensing and Ventures, Duke University.

Specific terms were not disclosed, but include equity, upfront and milestone-driven payments, and sponsored research commitments from StrideBio to Duke University, along with royalties on future product sales.

About StrideBio Founded in 2015 based on the groundbreaking research of Mavis Agbandje-McKenna, Ph.D., and Aravind Asokan, Ph.D., StrideBio, Inc., is a fully integrated gene therapy company focused on creating best-in-class genetic medicines with life-changing or curative potential for children and adults. Our proprietary structure-inspired adeno-associated viral (AAV) vector engineering platform (STRIVE) creates unique and differentiated capsids that overcome current limitations of first-generation gene therapies. Key targeted improvements include reduced seroprevalence, improved tropism for specific cell types, liver de-targeting and increased gene transfer efficiency, with the potential for improved safety and reduced doses in the clinic. StrideBio is advancing a robust pipeline of gene therapy candidates enabled by these novel engineered capsids, initially focused on genetically defined CNS and cardiovascular disorders. Combined with our genetic construct design expertise and in-house manufacturing capability at a 1000L scale, we are well positioned to advance novel best-in-class AAV gene therapies. StrideBio is based in a state-of-the-art 40,000-square-foot facility in Research Triangle Park, N.C., which houses our offices, research labs and in-house AAV manufacturing facilities. For more information, please visit http://www.stridebio.com or follow us on LinkedIn.

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StrideBio Announces a Multi-technology License and Master SRA with Duke University to Advance Next-generation Gene Therapies - BioSpace

Cell and gene therapies are overlapping fields of research and treatments. While both aim to treat and potentially cure diseases, they have slightly differing approaches and have different historical backgrounds. Due to growing interest surrounding this field, the general public still has much to learn and understand about each of these potentially life-saving therapies.

Below, we provide a general overview and brief historical context for each type of therapy.

Cell therapyis the process of replacing damaged or dysfunctional cells with new, healthy ones by transferring live cells into a patient. These can be autologous (also known as self-to-self, using cells from the patient receiving the treatment) or allogeneic (using cells from a donor for the treatment). While this field of treatment has recently begun to expand, some forms of cell therapy like the cancer-treating hematopoietic stem cell transplantation(HSCT) have been in practice for decades.

While many people have heard of bone marrow transplants, few realize that this procedure is a stem cell therapy. While stem cells can be derived from many sources, such as umbilical cord blood and mobilized peripheral blood, bone marrow derived stem cell therapy is the most commonly used today and has been for more than 50 years.

The first transfusion of human bone marrow was given to a patient with aplastic anemia in 1939. After World War II researchers diligently worked to restore bone marrow function in aplasia patients caused by exposure to radiation produced by the atomic bomb. After a decade of work they were able to show, in a mouse model, that aplasia could be overcome by bone marrow treatment.

The first allogeneic HSCT, which led the way to current protocols, was pioneered by E. Donnall Thomas and his team at the Fred Hutchinson Cancer Research Center and reported in the New England Journal of Medicine in 1957. In this study six patients were treated with radiation and chemotherapy and then received intravenous infusion of bone marrow rich stem cells from a normal donor to reestablish the damaged or defective cells. Since then the field has evolved and expanded worldwide. While almost half of HSCT are allogeneic, the majority of HSCT are autologous, the patient's own stem cells are used for treatment, which carries less risk to the patient.

In 1988, scientists discovered that they could derive stem cells from human embryos and grow the cells in a laboratory. These newly derived stem cells, referred to as embryonic stem cells (hESCs), were found to be pluripotent, meaning they can give rise to virtually any other type of cell in the body. This versatility allows hESCs cells to potentially regenerate or repair diseased tissue and organs. Two decades after they were discovered, treatments based on hESCs have been slow in coming because of controversy over their source and concerns that they could turn into tumours once implanted. Only recently, testing has begun as a treatment for two major diseases: heart failure and type 1 diabetes.

In 2006, researchers made a groundbreaking discovery by identifying conditions that would allow some cells to be 'reprogrammed' genetically. This new type of stem cell became known as induced pluripotent stem cells (iPSCs). Since this discovery, the field has expanded tremendously in the past two decades. Stem cell therapies have expanded in use and have been used to treat diseases such as type 1 diabetes, Parkinson's and even spinal cord injuries.

There has also been a growing focus on using other immune cells to treat cancer. Therapies such as CAR T-cellare dependent upon a patient's T-cells, which play a critical role in managing the immune response and killing cells affected by harmful pathogens. These cells are then reengineered to target and kill certain cancerous cells. Several CAR T-cell therapies have been FDA approved, with the first approval being given in 2017 for Yescarta and Kymriah, to be used for the treatment of B-cell leukemia in children and young adults.

Gene therapyis a process that modifies the expression of a gene or alters the biological process of living cells for therapeutic use. This process can take the form of replacing a disease-causing gene with a new, healthy one, inactivating the mutated gene, or introducing a new gene to help the patient's body fight a disease.

While the use of gene therapy to treat humans is fairly new, the science behind it has been used in science for decades. Farmers and geneticists have collaborated for years on crop improvement using cross pollination, genetic engineering and microinjection techniques to create stronger, more resilient crops.

The first human patient to be treated with gene therapy was a four-year old girlsuffering from severe combined immunodeficiencyin 1990. She received treatment for a congenital disease called adenosine deaminase (ADA). Since then, gene therapies have been used to treat diseases such as cancer, cystic fibrosis and hemophilia.In 2017, the FDA gave its first approval of a gene therapy called Luxturna, which is used to treat patients with established genetic vision loss that may result in blindness. Gene therapies are still being studied and developed, with over 1,000 clinical trialscurrently underway.

ThermoGenesis Holdings Inc., is a pioneer and market leader in the development and commercialization of automated cell processing technologies for the cell and gene therapy fields. We market a full suite of solutions for automated clinical biobanking, point-of-care applications and large-scale cell processing and manufacturing with a special emphasis on the emerging CAR-T immunotherapy market. We are committed to making the world a healthier place by creating innovative solutions for those in need.

For more information on the CAR-TXpress multi-system platform, please contact our Sales team.

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Thermogenesis Holdings Inc. published this content on 13 April 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 13 April 2021 07:10:03 UTC.

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ThermoGenesis : The History of Cell and Gene Therapy - marketscreener.com

The U.S. Food and Drug Administration approved the start of a first clinical trial of CRISPR_SCD001, the first non-viral and CRISPR/Cas9-based gene editing therapy for sickle cell disease(SCD).

Both the therapy and the upcoming Phase 1/2 trial planned to start this summer are the result of a collaboration between the Innovative Genomics Institute (IGI) and the University of California (UC), Los Angeles (UCLA).

IGI, a joint research initiative between UC Berkeley and UC San Francisco (UCSF), was founded by Berkeleys Jennifer Doudna, PhD. Doudna,along with Emmanuelle Charpentier of France, was awarded the 2020 Nobel Prize in Chemistry for groundbreaking work on the CRISPR-Cas9 gene editing tool.

Similar to the editing system used by bacteria as a defense mechanism, CRISPR-Cas9 allows researchers to edit parts of the genome by adding, removing, or changing specific sections of DNA.

We are motivated to work towards a cure that can be accessible and affordable to patients worldwide, Doudna said in a press release.

The launch of this trial is an essential first step on that path, added Doudna, who first approached the team at UCSF Benioff Childrens Hospital Oakland with the idea of developing a CRISPR/Cas9-based cure for SCD in 2014.

CRISPR_SCD001 uses the power of the CRISPR-Cas9 gene editing system to replace the mutatedHBB gene in a patients hematopoietic stem cells with a healthy version. The HBB gene, whose mutation cause SCD, provides the instructions to produce the beta subunit of hemoglobin, a protein found in red blood cells that transports oxygen.

These stem cells, which can give rise to all types of blood cells, are collected from a patients bone marrow, genetically modified in the lab with the innovative tool, and then returned to the patient in the form of a stem cell transplant.

By restoring production of normal hemoglobin and preventing red blood cells from becoming damaged and acquiring a sickle shape, the therapy is expected to be a potential cure for SCD.

Mark Walters, MD, the trials principal investigator and a professor of pediatrics at UCSF, said the goal of this form of genome-editing therapy is to correct the mutation in enough stem cells so the resulting blood in circulation has corrected red blood cells.

Based on previous bone marrow transplants, we predict that correcting 20% of the genes should be sufficient to out-compete the native sickle cells and have a strong clinical benefit, added Walters, who is also director of the blood and marrow transplant program at Benioff Childrens Hospital Oakland.

Unlike other investigational gene editing approaches for sickle cell, CRISPR_SCD001 delivers the CRISPR-Cas9 machinery to cells without relying on a virus as a transport agent. Its method, called electroporation, uses electrical pulses to create temporary pores in cell membranes that allow for the gene-editing tool to enter.

As such, the upcoming Phase 1/2 trial (NCT04774536) will mark the first attempt to correct the faulty HBB gene in a patients own cells with non-viral delivery of CRISPR/Cas9 gene correction tools.

The four-year study will evaluate the safety and effectiveness of a single dose of CRISPR_SCD001 in up to nine patients with severe SCD, ages 1235, who will be recruited at UCLA and Benioff Childrens Hospital Oakland.

If the therapy is found to be safe in the first six treated patients, all adults, the trial will proceed to enroll three adolescents, ages 1218, to evaluate its safety in younger patients.

This therapy has the potential to transform sickle cell disease care by producing an accessible, curative treatment that is safer than the current therapy of stem cell transplant from a healthy bone marrow donor, Walters said.

If this is successfully applied in young patients, it has the potential to prevent irreversible complications of the disease, he added.

Donald Kohn, MD, the principal investigator at the UCLA trial site and who will oversee all therapy manufacturing for the study, said that in theory, gene therapy and gene-editing approaches should be much safer than a transplant from another person and could become universally available because they eliminate the need to find the needle in a haystack that is a matched stem cell donor.

Kohn, who has also been involved in the development of several gene therapies for other diseases, is a distinguished professor of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA and a member of the UCLA Broad Stem Cell Research Center.

It is noteworthy that this new trial comes from a consortium of not-for-profit academic institutions incentivized with a long-term vision to cure the disease with an affordable solution that can globally benefit everyone who needs it, said Fyodor Urnov, PhD, IGIs director of technology and translation, who will oversee the trials bioinformatics and genomics activities.

Marta Figueiredo holds a masters in evolutionary and developmental biology and a PhD in biomedical sciences from the University of Lisbon, Portugal. Her research is focused on the role of several signaling pathways in thymus and parathyroid glands embryonic development.

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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that made up the lining of blood vessels found in the umbilical cord of newborns.

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1st CRISPR Gene Editing Trial Slated to Open in Severe SCD Patients - Sickle Cell Anemia News

In a long-term follow-up of an early-phase trial examining CD19.28 chimeric antigen receptor (CAR) T-cell therapy, the use of consolidative allogeneic hematopoietic stem cell transplant (alloHSCT) was associated with long-term and durable disease control in children and young adults with B-cell acute lymphoblastic leukemia (B-ALL).

These results were based on a cohort of 20 patients who were initially treated in a dose-escalation part of a phase 1 trial (NCT01593696) examining anti-CD19 CAR T-cell therapy in patients between 1 and 30 years who have not responded to standard treatment, plus an additional 30 patients who were treated in an expansion portion. The median follow-up for all patients examined was 4.8 years and represents the longest time period examined for the use of this therapy in children and young adults with B-ALL.

We demonstrate that CD19.28 CAR T cells followed by a consolidative alloHSCT can provide long-term durable disease control in [child and young adult patients] with relapsed or refractory B-ALL, wrote the study investigators who were led by Nirali N. Shah, MD. Following alloHSCT, we observed a significant long-term [event-free survival (EFS)] with an apparent plateau and a low relapse rate, providing support for this sequential approach for long-term cure.

The complete response rate (CR) was 62.0%, with 28 of the 31 patients achieving this end point also reaching minimal residual disease (MRD) negativity by flow cytometry. The rate of CR was higher in patients with primary refractory disease (P = .0035), fewer prior lines of therapy (P = .033), and an M1 marrow (P = .0007). Additionally, CR rates were better for patients who received fludarabine/cyclophosphamidebased lymphodepletion versus other regimens, at 69% and 25%, respectively (P = .041).

The median overall survival (OS) for the cohort was 10.5 months (95% CI, 6.3-29.2 months). The median EFS was 3.1 months (95% CI, 0.9-7.7), with rates at 3 and 6 months of 52.0% (95% CI, 37.4%-64.7%) and 38.0% (95% CI, 24.8%-51.1%), respectively. Notably, median EFS was not reached in patients treated with M1 marrow versus 0.9 months in those with M2 marrow (P .0001).

Of the patients achieving MRD-negative CR (n = 28), 21 (75.0%) went on to receive consolidative alloHSCT, with a median time to transplant of 54 days from infusion (range, 42-97). The median OS from transplant day 0 was 70.2 months (95% CI, 10.4 months-not estimable) and the median EFS was not reached. The rate of EFS at 5 years was 61.9% (95% CI, 38.1%-78.8%). There were 8 deaths between 0.8 and 71 months following alloHSCT, which included transplant-related complications and/or graft-versus-host disease or infection in 6 patients and 1 patient with a complication of secondary malignancy at 3 years post-transplant. Teo patients relapsed after alloHSCT, with a cumulative risk of relapse was 4.8% (95% CI, 0.3-20.3) and 9.5% (95% CI, 1.5%-26.8%) at 12 and 24 months, respectively, with death as a competing risk.

Of note, achieving a CR was associated with greater CAR T-cell expansion and grade 3/4 cytokine release syndrome (CRS). Overall, CRS occurred in 70.0% of patients, with 9 (18.0%) having a grade 3/4 event. Neurotoxicity occurred in 10 patients (20.0%), with 4 having severe neurotoxicity.

Central nervous system involvement was effectively treated with CAR T-cell therapy all patients with a marrow response and CRS, although 1 patients did have residual disease by flow cytometry at low levels.

The authors noted that given these findings, CD19-directed CAR T-cell therapy may be considered as a bridge to alloHSCT versus standard-of-care blinatumomab (Blincyto).

Despite its more ready availability, which is not dependent on manufacturing time or success thereof, the efficacy of blinatumomab in children is lower than in adults receiving blinatumomab and also lower than remission rates following CD19-CAR T cells, using any construct, particularly for those with high-burden disease, the study author wrote. Therefore, selection of CAR T cells over blinatumomab may be advantageous in patients with higher-burden disease and [extramedullary] disease or as a salvage for blinatumomab nonresponders.

References

Shah NN, Lee DW, Yates B, et al. Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL. J Clin Oncol. March 25, 2021. doi: 10.1200/JCO.20.02262

Originally posted here:
Transplant After CD19 CAR T-Cell Therapy Shows Durable Disease Control in Children, Young Adults With B-ALL - Cancer Network

Published on April 2, 2021

Recently, a 43-year-old man was presented at Fortis Hospital, Noida, complaining of severe back pain. Upon investigation, it was found that he was suffering from a rare disease, multiple myeloma which is a type of cancer that forms in the white blood cells or plasma cells. Here cancerous plasma cells accumulate in the bone marrow and crowd around the healthy blood cell that help in fighting infections by building antibodies, this puts the patients life at high risk. He therefore urgently required a Bone Marrow Transplant (BMT). Dr Rahul Bhargava, Director and Head, Hematology and Bone Marrow Transplant, Fortis Hospital, Noida and his team took a timely decision to go ahead with BMT to save his life.

A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Bone marrow is the soft, fatty tissue inside your bones. The bone marrow produces blood cells. Stem cells are immature cells in the bone marrow that give rise to different blood cells. Bone marrow transplant has now revolutionised. It is like a peripheral blood stem cell transplant, meaning, it is just like a blood transfusion (like platelet apheresis) which does not require any anesthesia.

Upon further investigation it was revealed that chemotherapy was required before BMT. Following the chemotherapy, on the 10thday of admission the team of doctors engulfed stem cells in the patients body which provided the body with a new source of healthy cells. Safe hospital environment and the doctors expertise in the area ensured that the BMT was done smoothly, without any complications and within 15 days the patient had been discharged. Usually, a patient takes 25-30 days to recover but here, due to patients will to recover and the facilities provided to him in the hospital he recovered at a faster pace.

Dr Rahul Bhargava, Director and Head, Hematology and Bone Marrow Transplant, Fortis Hospital, Noida, said,The case was complicated as the patient was suffering from high-risk multiple myeloma, which is a rare form of cancer. We took the necessary precautions and performed chemotherapy first to which he responded well and post that a Bone Marrow Transplant (BMT) was performed successfully. The process was smooth, and no complications arose during the same. We request patients to not fear BMT and undergo the process when required.

Talking about the clinical excellence at Fortis Hospital, NOIDA,Mr Hardeep Singh, Zonal Director, Fortis Hospital, Noidasaid, The team at Fortis Hospital, Noida try their best to save lives and do not give up even if there is 1% chance of survival. The patient was suffering from high-risk multiple myeloma for which immediate bone marrow transplant was required. The case was managed extremely well and with a lot of patience by Dr Rahul Bhargava and his team. I applaud the team of doctors for their continued commitment towards clinical expertise and patient care.

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Timely Bone Marrow Transplant by Fortis gives new lease of life to a patient with Multiple Myeloma - APN News

Actress Kirron Kher is suffering from Multiple Myeloma, a type of blood cancer. Read to know the causes, symptoms, treatment, risks and more about the fatal disease.

New Delhi | Jagran Health Desk:Kirron Kher is suffering from Multiple Myeloma which is a type of blood cancer. The actress's husband Anupam Kher made an official announcement about her illness through a post on his official social media handle.

He wrote,"Just so that rumours don't get the better of a situation Sikandar and I would like to inform everyone that Kirron has been diagnosed with multiple myeloma, a type of blood cancer. She is currently undergoing treatment and we are sure she weill come out of this stronger than before. We are are very blessed that she is being looked after by a phenomenal set of doctors. She's always been a figher and takes things head on. She's all heart nd that's why she has so many people that love her. So keep sending your love to her in your prayers and in your heart. She is well on her way to recovery and we thank everyone for their support and love. Anupam and Sikander."

What is Multiple Myeloma?

Multiple Myeloma is a progressive hematologic disease. It is a cancer of plasma cells, which are type of blood cells in the bone marrow. When cells multiply unconditionally, they crowd out normal cells, therefore the body does not work the way it should. This disease causes damage to the immune system, bones, red blood cells etc. Cancerous plasma cells gather in the bone marrow, produce abnormal proteins, which causes complications.

What are the symptoms of Multiple Myeloma?

When the disease is in its early stage there may be no signs of symptoms as such. But some of the visible symptoms of this disease are as follows:

Diagnosis of Multiple Myeloma

Doctors advise diagnostic tests considering many factors such as:

Tests of Multiple Myeloma

Here are some of the tests which are done for diagnosis of multiple myeloma:

Causes of Multiple Myeloma

Although the causes of myeloma are not very clear. But, the disease occurs when abnormal cells multiply rapidly, they accumulate and crowd out healthy blood cells. Abnormal antibodies (monoclonal protein or M proteins) produced by myeloma cells cause problems, such as damage to kidneys, bones etc.

Complications during Multiple Myeloma

Risk Factors ofMultiple Myeloma

Treatment ofMultiple Myeloma

Treatment of Multiple Myeloma includes medication, chemotherapy, radiation, corticosteroids, stem-cell transplant etc.

Posted By: Sanyukta Baijal

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Kirron Kher is suffering with Multiple Myeloma: Know the causes, symptoms and more about this type of blood cancer - Jagran English

The use of decitabine was linked to improved platelet counts and survival rates in patients with refractory prolonged isolated thrombocytopenia (RPIT), which can be a complication of allogeneic hematopoietic cell transplantation (HCT), according to the results of a study recently published in Blood Advances.

Isolated thrombocytopenia is a frequent and severe complication of HCT that is associated with worse outcomes, the study investigators explained in their report. According to the investigators, RPIT has been thought to relate to such factors as disease recurrence, treatment history, factors related to the transplant donor, and other transplantation complications. However, they suggested that the absence of a consistent definition for prolonged isolated thrombocytopenia has hindered understanding of its patterns.

This prospective, phase 3 clinical trial (ClinicalTrials.gov Identifier: NCT02487563) included patients who had undergone allogeneic HCT and developed RPIT and who were treated at any of 6 participating hematology centers in China.

Patients were randomly assigned across 3 treatment arms: low-dose decitabine with recombinant human thrombopoietin (arm A), decitabine only (arm B), or conventional treatment (arm C). Platelet response at 28 days following treatment was the primary study endpoint, and this was defined as a sustained increase of 30 x 109/L or more, independent of transfusion for 3 days.

Across the participating centers, 2616 allogeneic HCT recipients were identified, of whom 256 had developed thrombocytopenia for more than 60 days following transplantation, and 97 met criteria for study inclusion. A total of 91 patients were evaluated for response.

The response rate for arm A was 66.7%, for arm B it was 73.3%, and for arm C it was 19.4%. Arms A and B were not statistically different for response (P =.779), while the response rate for arm C was statistically lower than the others (P <.001).

At a median follow-up of 11 months, the estimated 1-year survival rates were 64.4% for arm A and 73.4% for arm B, which were both greater than in arm C (41.0%). When the decitabine arms were combined, the survival rate was 68.2%, which was significantly higher than 1-year survival in arm C (P =.008).

The treatment arms receiving decitabine also showed significantly elevated total megakaryocyte counts, platelet-shedding megakaryocytes, and megakaryocyte polyploidy, while arm C did not. This suggested there are improvements in megakaryocyte proliferation and maturation with decitabine, according to the investigators.

In conclusion, this multicenter randomized study demonstrates the efficacy and safety of decitabine for patients with RPIT after HCT, with improved response and prolonged survival, the study investigators wrote in their report.

Reference

Tang Y, Chen J, Liu Q, et al. Low-dose decitabine for refractory prolonged isolated thrombocytopenia after HCT: a randomized multicenter trial. Blood Adv. 2021;5(5):1250-1258. doi:10.1182/bloodadvances.2020002790

Read the original here:
Decitabine Improved Outcomes for Patients With Refractory Prolonged Isolated Thrombocytopenia - Hematology Advisor

Lake in the Hills Police Officer Mike Domagala with one of his children. | Provided Photo.

A Lake in the Hills police officer with 20 years of service, who is a father of four kids, says he will no longer be able to work as he battles a rare blood cancer, and a fundraiser has been started for him.

Mike Domagala began his law enforcement career in Fox River Grove in 2002. He was hired by the Lake in the Hills Police Department in 2012.

Domagala, 43, was diagnosed in July with multiple myeloma, which is a rare blood cancer that is not curable but is treatable.

According to the Mayo Clinic, cancerous plasma cells accumulate in the bone marrow and crowd out healthy blood cells. The cancer cells produce abnormal proteins that can cause complications.

Domagala is married and has four children, ages 5, 12, 16, and 23. At the onset of the cancer discovery, he had to have a pelvic biopsy, two bone marrow biopsies, blood work, PET scans, CT scans, and MRIs, according to a GoFundMe account.

Domagala has undergone multiple cycles of chemotherapy that started on August 4 and then a stem cell transplant in December.

He has not been able to patrol as an officer since his diagnosis. On March 25, Domagala said in an update that he had his 100-day post bone marrow appointment, which went well.

I also had my hematologist appointment for my maintenance therapy which will be a chemo pill every day and a bone healing transfusion once a month. The overwhelming support my family and I have received through this has been amazing and helps me continue to fight through this difficult time, he said.

Domagala said in February that he was optimistic about getting back to work. However, he said in his March 25 update that his doctor told him he would not be able to return to working the streets as a police officer.

I have been a police officer for almost 20 years and have always wanted to be since I was a child. I have no idea what I am going to do but I will figure it out as this is still sinking in, he said.

Fellow police officer Erik Watters started a GoFundMe account for Domagala in November and it continues to bring in donations from the public.

The fundraiser money is going towards uncovered medical expenses, travel expenses for treatments and to help his family with everyday expenses.

Mike maintains a strong fighting spirit and finds his strength in his love for his family. Mikes greatest concern is in continuing to provide for his family while he covers all of his uncovered medical expenses, Watter said.

The GoFundMe has a $50,000 goal and has raised $28,800 so far as of Thursday.

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Lake in the Hills police officer and father of 4 kids battling rare cancer forced to retire - Lake and McHenry County Scanner

The pancreas, saysGary Lewis, an endocrinologist at Toronto General Hospital and director of the Banting & Best Diabetes Centre at the University of Torontos Temerty Faculty of Medicine, is like an exquisitely sensitive and perfectly networked computer.

Second by second,he notes,the pancreassecretesjust the right amount ofinsulinor glucagontolower or raiseblood sugarintotheportal veinthat leadsdirectlyto the liver, the site of key metabolic processes. Insulingis then distributedto every tissue in the body via general circulation.

Thats one reason a cure for diabetes has proven elusive 100 years after the discovery of insulin.

Another big reason is the complexity of how the disease arises. In type 1 diabetes, the immune system destroys the insulin-producing beta cells of the pancreas, creating a life-threatening spike in blood sugar. Type 2 diabetes usually comes on more slowly, as the body becomes resistant to insulin or the pancreas cant produce enough of it.

Genetics play a role in both types. Exposure to viruses and other environmental effects may be a factor in type 1. Lifestyle factors, including weight gain and physical inactivity, are strongly linked to type 2.

The bottom line, says Lewis, is that diabetes is a multifactoral disease, and were not close to a cure.

Ask about treatments, though, and Lewis gets excited.

The last two decades have brought a plethora of clinical and research advances, from new drugs to boost and sensitize the body to insulin and promote weight loss, to lifestyle interventions that improve diet, continuous monitoring of blood sugar, long- and short-lasting insulin, better insulin pumps, pancreatic transplantsand pre-clinical stem cell and immunosuppressive therapies.

Progress on treatments has been fantastic, especially for type 2, Lewis says. Im very, very hopeful.

The distinction between treatment and cure in medicine is often unclear. And for the 3.6 million Canadians living with diabetes, the distinction matters less and lessif the goal is a full and healthy life.

Type 2 diabetes accounts for about 90 per cent of diabetes cases in Canada. Prevalence is rising, but Canadians with type 2 diabetes are living longer and have fewer diabetes-related complications.

The clinic doesnt look like it did 30 years ago, says Lewis, who mainly treats patients with type 2. We see fewer amputees, less blindness. Patients are generally healthier, and their prognosis is often excellent if they maintain their blood sugar target and other key parameters.

Weight loss is a cornerstone of treatments to lower blood sugar, and recent research has strengthened the link between weight reduction and type 2 diabetes management. Some people with type 2 can lose weight and control blood sugar through dietary changes and exercise alone.

Bariatric surgery is very effective for weight loss and often results in diabetes remission, although it comes with surgical risks and is expensive.

If we could prevent obesity, we could greatly reduce the incidence of type 2, Lewis says. And experiments have shown wecan get a remission withlifestyle changes, so we know what works.

The problem is broad implementation.

Ive tried to lose weight and I know how difficult it can be, especially in an environment of convenient and inexpensive calories, Lewis says. Moreover, factors such as income, education, ethnicity, access to healthy food and living conditions can make lifestyle changes that curb obesity nearly impossible.

Social determinants of health are overwhelmingly the most important influence on who gets type 2 diabetes, and how well or poorly they do with it, Lewis says.

Fortunately, dozens of new drugs for diabetes have hit the market in the last two decades.

Medications for weight loss round out the armamentarium, and some also protect against kidney damage and lower cardiac risk. Current therapies can reduce body weight up to 10 per cent, although a loss of 20 per cent or more would have a greater effect on outcomes for patients with type 2 diabetes, saysJacqueline Beaudry, an assistant professor of nutritional sciences at U of T who studies links between obesity, hormones and diet.

Beaudry is probing the biology that underpins these medications, including the gut hormones GLP-1 and GIP. They control blood glucose and reduce appetite, but scientists are unsure how.

If we could understand their mechanisms of action, we could design better drugs, Beaudry says.

For people with type 1 diabetes, continuous glucose monitors, insulin pumps and even automated closed-loopsystems that run on mobile apps to deliver insulin as-needed have radically changed the patient experience.

Sara Vasconcelos left),an assistant professor at U of Ts Institute of Biomedical Engineering, has worked withCristina Nostro (right), an associate professor in the department of physiology,and her team in the McEwen Stem Cell Institute at UHNto extend the survival and functionality of pancreatic precursor cells generatedfrom human stem cells.

Cell therapy could prove more liberating still.

University labs and biotechs are working on implantable devices that house insulin-producing cells derived from stem cells.

To that end,Cristina Nostro, an associate professor in the department of physiology in the Temerty Faculty of Medicine,and her team in the McEwen Stem Cell Institute at University Health Network recently discovered a more efficient way to generate and purify pancreatic precursor cells from human stem cells in the lab.

They have also found a way to vascularize those cells by working withSara Vasconcelos, an assistant professor at U of Ts Institute of Biomedical Engineering. Together, they have extended the survival and functionality of the cells in animal models of diabetes.

The biggest problem with these therapies is that the immune system rejects them. The same challenge currently hinders pancreas and islet transplants.

The immune system is an amazing machine, were luckyits so good, says Nostro. But its very difficult to control when it goes awry, as in autoimmune conditions.

Nostro is working with immunologists at the university on a method to protect insulin-producing beta cells from immune rejection, and she says many researchers in the field are now focused on immune-protective approaches.

Another strategy for type 1 diabetes is to tamp down the autoimmune response before the disease progresses. The idea is to prevent immune cells that damage the pancreas while the body still produces beta cells.

Groups around the world are bringing different ideas and creative approaches to treat type 1 diabetes, thats the beauty of science, says Nostro. I am very hopeful about what the future holds. Who knows? Maybe we will see hybrid technologies combining a pump and cells. We have to keep an open mind.

This story was originally published in U of T Med Magazines Insulin Issue.

Original post:
Insulin 100: How the road to a diabetes cure is yielding better treatments - News@UofT

Boxcar scars are a type of acne scars which look like round, oval depression. As the scars are of different types, for example, based on redness, depth or location, its treatment also varies. Microdermabrasion, Dermabrasion, Fillers, Chemical Peels, Laser Therapy, Microneedling, Punch Excision, and Subcision, are some of the treatments required for treating boxcar scars. As these scars cant go away of their own, People considering the treatment is growing.

Growing Preference for Micro needling and Ablative Lasers

The ablative lasers are considered as the gold standard for treating acne scars, patients have witnessed a 75% improvement in atrophic acne scars at 18 months after this high energy carbon dioxide laser treatment. The technique when used on dark skinned people showed good to excellent results in 74%, however hyper pigmentation was witnessed among 29% of patients. Due to its long time recovery process and various side effects, the ablative lasers have become less popular.

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Of late, microneedling is gaining momentum as they provide the best cosmetic outcomes. Due to its collagen inducing effect, the encouraging results prove that microneedling is an effective and inexpensive method for dealing with boxcar scars. It takes very less time for recovering, a study found that only after 3 treatments, patients can visibly see the positive effect in their scarring and is relatively risk free. Microneedling can be performed with a dermaroller or a microneedling pen. Microneedling involves puncturing the skin multiple times using needles, a tattoo gun or roller. When microneedling is combined with platelet rich plasma or glycolic acid peels, improvement in acne scar improved up to 62%.

Emerging Technologies Can Boost Adoption of Boxcar Scar Treatment

Researchers and scientists are always on the motion of developing and introducing new and more effective treatments for replacing the traditional therapies. For instance, a latest technology for the treatment of scarring is laser speckle contrast imaging (LSCI). LSCI helps in detecting the backscatter which eventually detects the blood flow by illuminating the tissue with its coherent laser light. The technique is relevant for scarring because the healing process of scarring requires adequate tissue perfusion. LSCI can also be used to treat patients with burn wounds as it detects the severity of partial thickness in wounds.

Complications in Laser Therapy

Side effects due to laser therapy such as burns, dyspigmentation and infection may happen after the laser treatment. Laser treatment has a risk of overheating the tissue through excessive heat generation or by a failure of the cooling techniques. The risk of burns is higher for lasers that use a continuous beam. Risk of dyspigmentation is higher in dark skinned or tan individuals. Due to such side effects, the treatment by laser may go back scale. However, latest innovations in the sector may help in mitigating the issue.

Competitive Landscape

The key players in the market include Merz, Inc., Cerave, Lumenis, Enaltus LLC, Scarsheal, Inc., CCA Industries, Proactiv Company, Cynosure, Inc., PCA Skin, Solta Medical, Smith and Nephew plc, Scarheal, Inc., NewMedical Technology, Inc., Bausch Health, Suneva Medical, Inc., Sonoma Pharmaceuticals, Inc., etc.

Latest development by doi.org shows 755nm picosecond Alexandrite laser has been effective in patients with acne scars. In the split face study, people were treated with laser in half of their face and that half showed effective improvement results in Post inflammatory erythema and acne scars. Patients stated that treatment was tolerable, with only mild erythema discovered as a side effect.

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A study reported in the Journal of cosmetic dermatology in February 2020 by Darrow Stem Cell Institute demonstrated that platelet rich plasma shows better response, fewer side effects, and shorter downtime as compared to combined subcision and PRP. The experiment was performed on 45 patients with atrophic acne scars by dividing the group into 3 and giving intradermal injection to first group, chemical reconstruction of skin scars was performed on second group and combined skin needling and PRP was performed on the third group. The third group witness significant improvement without any major side effect thus, reaching to the conclusion that PRP is beneficial for acne scars.

PICOCARE 450 is a US FDA approved machine developed by WonTech for laser skin care treatment. The innovative machine is responsible for treating all skin types, show faster visible results in less sitting. The technology targets only the pigment to be removed and is suitable for treating chickenpox scars, ice pink scars, boxcar scars, acne scars, etc.

Regional Outlook

According to WHO, scars affect almost 80-90% of teenagers in the western world. As per the study by National Library of Medicine, boxcar scars are prevalent and is almost in 54% population as post acne scar. Thus, rising incidences of burn cases and also increasing prevalence of boxcar scar cases is expected to drive the market during the forecast period. According to the survey by Harris Poll around 10 million patients who have had dermal filler have experienced filler treatment a good option, thus, its demand is also one of the factor for the boost of boxcar scar market.

Asia Pacific is also leading market for the boxcar scar treatment. Due to increased incidences of burns in India having a record of 70lakh burn injury cases every year, the adoption of treatment is also expected to surge. Rising awareness about the treatment of scars is yet another factor boosting the growth. Japan in Asian region is an ideal market due to availability of various treatment options owing to the increase in health care expenditure.

UK is a major contributor to the European market. According to British Association of Plastic, rising number of plastic surgery units in UK is fuelling the adoption of large number of incidences. Microneedling as a treatment is escalating in Europe owing to its benefits for skin tightening, better skin texture, scar reduction, improved skin tone, etc. Moreover, growing adoption of anti-ageing procedures, and awareness regarding the treatments is escalating the market further.

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Segmentation

By Treatment Type

By Laser Product

By End-user

By Region

Key Questions Answered

Carbon dioxide and Pulse dyed laser are some of the laser products used for boxcar scar treatment

Proactiv Company, Cynosure, Inc., PCA Skin, Solta Medical, Smith and Nephew plc, Scarheal, Inc., NewMedical Technology, Inc., Bausch Health, etc.

Latest innovations, growing awareness regarding the treatment, and comfortable treatment is giving people the confidence to treat.

US, UK, France, Germany and Italy are some of the largest markets for boxcar scars

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Boxcar Scars Market |Exclusive Report on Latest Trends and Market Growth Opportunities - BioSpace

KENILWORTH, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending that the European label for KEYTRUDA, Mercks anti-PD-1 therapy, be updated to include data from KEYNOTE-361, a Phase 3, open-label trial that evaluated KEYTRUDA as a monotherapy and in combination with chemotherapy for the first-line treatment of certain patients with advanced or metastatic urothelial carcinoma. In Europe, KEYTRUDA is approved for the treatment of adult patients with advanced or metastatic urothelial carcinoma (bladder cancer) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 with a Combined Positive Score (CPS) 10. This approval was based on a single-arm study, KEYNOTE-052; KEYNOTE-361 was conducted as part of a post-marketing commitment following the initial approval of KEYTRUDA for these patients.

As previously announced, KEYNOTE-361 did not meet its primary endpoints of progression-free survival (PFS) and overall survival (OS) for the combination of KEYTRUDA plus chemotherapy. However, the CHMP concluded that the benefit-risk profile remains positive and that including data from KEYNOTE-361 in the label allows physicians to evaluate the potential benefit-risk of KEYTRUDA on an individual basis.

KEYTRUDA has become an important treatment option for certain patients with locally advanced or metastatic bladder cancer in the European Union and other countries around the world, said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. We are pleased with todays positive opinion by the CHMP, which fulfills our post-marketing requirement for KEYTRUDA in these patients in the European Union and will enable continued access for patients in need of another treatment option.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,400 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS 10), as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% of these patients interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen, which was at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1). All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other antiPD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after antiPD-1/PD-L1 treatment. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between antiPD-1/PD-L1 treatment and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using antiPD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an antiPD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

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Merck Receives Positive EU CHMP Opinion for Updated Label of KEYTRUDA (pembrolizumab) To Include Results of Phase 3 KEYNOTE-361 Trial in Certain Adult...

NEW YORK, March 31, 2021 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (the Company or BeyondSpring) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and the China National Medical Products Administration (NMPA) for use of plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia (CIN). Plinabulin in combination with a G-CSF therapy, which received breakthrough therapy designation from the U.S. FDA and the China NMPA for concurrent administration with myelosuppressive chemotherapeutic regimens in patients with non-myeloid malignancies for the prevention of CIN, has the potential to raise the standard of care in CIN for the first time in 30 years.

CIN remains a severely unmet medical need. Treatment or prevention of CIN with G-CSF has been the standard of care since Neupogen was approved in 1991. The main benefit of G-CSF treatment, however, is in Week 2 after chemotherapy. Week 1 after chemotherapy is considered the neutropenia vulnerability gap where over 75% of CIN-related clinical complications occur, including febrile neutropenia, infection, hospitalization and death. Plinabulin is the first agent seeking FDA approval that has the potential to fill this gap by working in Week 1 to prevent the onset and progression of CIN. Therefore, combining plinabulin and G-CSF may maximize the protection of patients for the full cycle of chemotherapy, as demonstrated in the PROTECTIVE-2 Phase 3 registration study.

CIN is a major concern for physicians and their patients undergoing cancer treatment. Plinabulin provides benefits above and beyond what is currently available on the market and has the potential to be a game-changer for patients undergoing chemotherapy treatment, said Dr. Douglas Blayney, Professor of Medicine at Stanford University Medical School and global PI for CIN studies. CIN, which can lead to life-threatening infections, is the number one reason for the 4Ds in chemotherapy (Decrease, Delay and Discontinue dose and Downgrade regimen). We hope plinabulin will allow patients to better tolerate chemotherapy, thus enabling patients to stick to their optimal treatment plan and avoid serious CIN complications.

The NDA submission is based on positive data from BeyondSprings PROTECTIVE-2 Phase 3 registration study which showed that plinabulin in combination with pegfilgrastim demonstrated superior CIN prevention benefit, compared to pegfilgrastim alone. The study met the primary endpoint, with a statistically significant improvement in the rate of prevention of grade 4 neutropenia (improved from 13.6% to 31.5%, p=0.0015) and met all key secondary endpoints, including duration of severe neutropenia (DSN) and absolute neutrophil count (ANC) nadir. In addition, the combination reduced clinical complications such as incidence and severity of febrile neutropenia (FN) and incidence and duration of hospitalization for FN patients. The combination is well tolerated, with an over 20% reduction of grade 4 Treatment-Emergent Adverse Events (TEAE) in the combination compared to that of pegfilgrastim alone. The NDA submissions will include five supportive trials that show consistent CIN prevention in various chemotherapy regimens and cancers in over 1,200 patients.

This NDA submission is the culmination of years of research to prove that plinabulin can improve the long-established standard of care and address an unmet medical need to further alleviate the risk burden of CIN for patients receiving chemotherapy, said Dr. Lan Huang, co-founder, CEO, and chairman of BeyondSpring. With CIN responsible for potentially delaying treatment and causing life-threatening infections, we hope that receiving the improved care represented by the plinabulin and G-CSF combination will allow patients to better tolerate chemotherapy and potentially see increased treatment success rates. We are grateful for the patients participation in plinabulins clinical trials and the participation and contributions of our investigators and our many other clinical partners.

Each year in the U.S., 110,000 patients receiving chemotherapy are hospitalized after developing CIN, a severe side effect that increases the risk of infection with fever (also called febrile neutropenia, or FN), which necessitates ER/hospital visits. Due to the COVID-19 pandemic, the updated National Comprehensive Cancer Network (NCCN) guidelines expanded the use of prophylactic G-CSFs, including pegfilgrastim, from high-risk patients only (chemo FN rate >20%), to include intermediate-risk patients (FN rate between 10-20%), to reduce the number of hospital/ER visits related to CIN. The revision of the NCCN guidelines effectively increases the addressable market of patients who may benefit from treatment with plinabulin, if approved, to approximately 440,000 cancer patients in the U.S. annually.

There is a large unmet medical need and a growing market for CIN prevention and treatment in China as well. According to Lancet Oncology, 60% of East Asia cancer patients are treated with chemotherapy1. In 2020, there were 4.6 million new cancer patients in China which could correspond to 2.8 million patients using chemotherapy and needing CIN prevention agents. According to IQVIA data, the G-CSF drug market (for CIN treatment) in China is growing at over 30% a year.

About PROTECTIVE-2 (Study 106) Phase 3 Registration Study The Phase 3 portion of PROTECTIVE-2 was a double-blind and active-controlled global registration study. It was designed as a superiority study to compare the safety and efficacy of plinabulin (40 mg, Day 1 dose) + pegfilgrastim (6 mg, Day 2 dose) versus a single dose of pegfilgrastim (6 mg, Day 2 dose) in patients with breast cancer, treated with docetaxel, doxorubicin and cyclophosphamide (TAC, Day 1 dose) in a 21-day cycle. TAC is an example of high FN risk chemotherapy and is the regimen used in all G-CSF biosimilar registration studies.

The primary endpoint was the rate of prevention of Grade 4 neutropenia and secondary endpoints included DSN and mean ANC nadir in Cycle 1. Literature shows that despite the use of pegfilgrastim, 83 to 93 percent of patients treated with TAC still suffer Grade 4 neutropenia (or rate of Grade 4 neutropenia prevention at 7-17%), which demonstrates the severe unmet medical need for improved treatment2,3.

The ANC data, which are used to calculate these endpoints, were obtained through central laboratory assessments by Covance Bioanalytical Methods using standardized and validated analytical tests. Covance was the clinical contract research organization (CRO) for patient recruitment and monitoring of global sites for this study.

About CINChemotherapy-induced neutropenia (CIN) is the primary dose-limiting toxicity in cancer patients who receive chemotherapy and is the primary cause for the 4Ds (Decrease, Delay, Discontinue dose and Downgrade regimen). The 4Ds lead to a decrease of the anti-cancer benefit of chemotherapy, e.g., >15% of dose reduction correlated to >50% survival reduction4. The National Comprehensive Cancer Network (NCCN) recently updated its treatment guidelines for CIN prophylaxis using G-CSFs to include both high- and intermediate-FN risk patients treated with chemotherapies, to preserve hospital and ER resources for COVID-19 patients, and to maximize protection from CIN. The NCCNs action effectively doubled the number of patients recommended to receive CIN prophylaxis.

About PlinabulinPlinabulin, BeyondSprings lead asset, is a selective immune-modulating microtubule-binding agent (SIMBA). A global Phase 3 clinical trial in CIN (PROTECTIVE-2) with plinabulin in combination with pegfilgrastim versus pegfilgrastim alone has been completed and is the basis for an NDA filing in the U.S. and China for the prevention of CIN. In this trial, plinabulin reduced the neutropenia vulnerability gap associated with G-CSF therapy alone. Additionally, a global Phase 3 study for the treatment of later-stage NSCLC in EGFR wild-type patients (DUBLIN-3) is now fully enrolled and will evaluate the combination of plinabulin and docetaxel versus docetaxel alone for overall survival in NSCLC patients. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells5,6 and the second is early-onset action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs)7. Effects on HSPCs could explain the potential for plinabulin not only to prevent CIN but also to increase circulating CD34+ cells in patients. As a pipeline in a drug, plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1 / PD-L1 antibodies.

About BeyondSpringHeadquartered in New York City, BeyondSpring is a global biopharmaceutical company focused on developing innovative immuno-oncology cancer therapies to improve clinical outcomes for patients who have high unmet medical needs. BeyondSprings first-in-class lead asset plinabulin is a pipeline in a drug. It is filed for approval in the US and China for the prevention of chemotherapy-induced neutropenia (CIN) and has a fully enrolled pivotal study to test an anti-cancer benefit with an overall survival primary endpoint in non-small cell lung cancer (NSCLC). Additionally, it is being broadly studied in combination with various immuno-oncology agents that could boost the effects of PD-1 / PD-L1 antibodies. In addition to plinabulin, BeyondSprings extensive pipeline includes three pre-clinical immuno-oncology assets and a subsidiary, SEED Therapeutics, which is leveraging a proprietary targeted protein degradation drug discovery platform.

References:

Investor Contact:Ashley R. RobinsonLifeSci Advisors, LLC+1 617-430-7577arr@lifesciadvisors.com

Media Contact:Darren Opland, Ph.D.LifeSci Communications+1 646-627-8387darren@lifescicomms.com

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BeyondSpring Announces Submission of New Drug Application to US FDA and China NMPA for Plinabulin and G-CSF Combination for the Prevention of...

Its something of the holy grailrun whole genome sequencing on a sample of a persons blood and identify their risk for disease, all quickly and affordably. Oxford, Englands Genomics, founded in 2014 out of Oxford University by Sir Peter Donnelly, may be getting close.

The company is launching a trial in a new NHS pilot project with 1,000 volunteers, focusing on heart disease. It also plans to begin a similar trial in Stanford Hospitals in California with about 5,000 patients between the ages of 40 and 60 starting this summer.

If effective, it would be able to help people in their 40s or 50s determine the likelihood of their developing heart disease. This would allow physicians to help patients make the appropriate lifestyle changes and begin taking necessary drugs, such as statins.

The volunteers in the studies will donate a blood sample and the Genomics technology platform leverages an algorithm to analyze their genetic patterns. Some of those patterns have been associated with an increased risk of heart attack later in life, even if they currently have no symptoms. They will then be given a personal polygenic risk score (PRS), which can be used alongside a clinical risk prediction tool that the NHS is already using, that takes into consideration things like BMI and cholesterol levels.

This is yet another example of the NHS leading the world with this trial, Donnelly told the Evening Standard. This is cutting edge [tech]. It is about getting it into healthcare now and increasing focus on prevention.

Although these studies are focusing on heart disease, the companys technology is also focused on a range of genetic patterns associated with other diseases, such as cancer and multiple sclerosis. Donnelly even thinks its possible that eventually it will be used to evaluate people in their 20s and 30s for diseases that are more commonly developed earlier, such as auto-immune diseases.

Of course, some people may not want to know.

I understand why someone would be a bit worried, Donnelly said. It is important to say that these are just risk factors. If you have a high PRS score for heart disease, you are around four to five times more likely to get it. Its not that genetics determine the outcome, it is a risk factor. In all cases, there are things you can do [to help prevent disease]. You can be more vigilant, you can have medical interventions. That is important to understand.

On March 1, Genomics completed a $30 million funding round, with investments from Foresite Capital and F-Prime Capital, joined by existing backers Oxford Sciences Innovation and Lansdowne Partners. The company plans to use the monies to expand its work building its health platform.

Jim Tananbaum, chief executive officer of Foresite Capital, stated, Genomics plc plays a key role in transforming how we understand and deliver precision medicine at scale. We are excited to support this talented management team as the company embarks on its next growth phase.

Stephen Knight, president and managing partner of F-Prime Capital, noted, The convergence of data sciences with life sciences is one of the most exciting areas in healthcare today and we see Genomics plc as a clear leader in that field. The companys proprietary research platform powered by a large dataset of genotypic and phenotypic information, combined with the leading statistical genomics team in the world, delivers unique insights in the discovery of new therapeutic targets as well as key advancements in preventative healthcare.

Read more here:
Oxford's Genomics Pushing the Boundaries of Personalized Medicine - BioSpace

Master Sgt. Geoff Dardia was nearly a decade into his Special Forces career when he says he hit a wall. He was struggling both mentally and physically to keep doing his job and couldnt explain why.

All of the sudden, I was just a shell of a person like everything you hear about feeling like youre dragging a dead body and losing your zest for life, Dardia said.

Plagued by severe migraines, fatigue and issues with his balance and vision, Dardia, now 44, sought help.

His superiors told him to visit a military behavioral health specialist and be treated for PTSD or depression, but Dardia was convinced his ailments were more than just psychological. So, he did what any good Green Beret would do and applied his training to research, analyze and attack the problem condition.

Following the steps of the military decision-making process, Dardia learned everything he could about his operational environment and the various ways it could affect him.

Traumatic brain injuries, toxic exposure to heavy metals and carcinogens, traumatic stress and sleep deprivation are unfortunately common occurrences for members of the special operations community.

After identifying the underlying causes for his symptoms, Dardia began planning a course of responsive action. The process was so simple, straightforward, and guided by existing military doctrine that it led him to question the Armys current approach to health care.

I was like, This is so easy. Why wouldnt we do this with health and wellness and medicine? Dardia said.

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At its core, thats what functional medicine is all about: finding and treating underlying causes of illness or pain. The Institute for Functional Medicine defines it as a systems biology-based approach that focuses on identifying and addressing the root cause of disease.

Also referred to as personalized, performance or lifestyle medicine, the approach is grounded in a philosophy of caring for a whole person made up of interconnected parts.

Its what Dardia and health care professionals spoke about on March 25 at the Warfighter Health Symposium in Tampa, Florida. Hosted by non-profits Task Force Dagger Special Operations Foundation and HunterSeven, the event served to informally educate active duty servicemembers, medical providers and veterans about the current issues and solutions in military health care. There were 50 people the maximum allowed under COVID-19 restrictions who attended.

After personally experiencing the difficulty of receiving holistic treatment, Dardia began making the changes he wanted to see. In 2012, when TFDSOF helped him through his personal health struggles, Dardia decided to give back by founding the organizations Health Initiative Program.

The program provides pathways and funding assistance for members of the military to seek treatment from outside health care providers and institutions in the field of personalized medicine.

Partnering with organizations like the Cleveland Clinic Center for Functional Medicine and becoming involved with active-duty health initiatives in the 3rd Special Forces Group, Dardia has been raising awareness of the power of preventative and holistic medicine for the better part of a decade now.

According to Dardia, the militarys current approach to health care is too reactive. Service members are treated for cancer or suicidal ideations or organ failures when such issues could have been prevented with proper countermeasures and education about their causes years earlier.

Just because you have mental health symptoms, doesnt mean mental illness is the cause, said Dr. Carrie Elk, founder of the Elk Institute for Psychological Health & Performance, a non-profit established to provide mental health education and treatment to servicemembers.

Elk has worked with SOCOM and the SOF community to treat operators for the underlying cause of post-traumatic stress disorder since 2010, when she first spoke at the Joint Special Operations Forces Senior Enlisted Academy on how PTSD works. Her practice now reaches both operators and members of the general military community.

They were applying the same stuff they used for mental illness to PTSD, but the problem is just the way the information is stored, said Elk. The audience was stunned by Elks presentation, and special operations personnel began filling the waiting room of her practice.

In just two hours of therapy, the doctor says, shes able to correct the storage of a traumatic memory.

In traumatic situations, according to Elk, memories are stored as sensory experiences. When servicemembers return home from traumatic environments, triggers like smells and sounds can bring them right back to places of anger, agitation, depression and anxiety.

Health care providers treating symptoms of depression and anxiety with prescription medications ignore the real problems at hand, according to Elk.

Were putting a Band-Aid on a bullet hole or at least trying to, said Elk. Youre not fixing the cause, youre just managing symptoms when you dont have to.

Functional approaches like Elks are growing in popularity. The Army adopted a section on holistic health in its updated physical fitness doctrine in September 2020 a combination of its previous initiatives like the Performance Triad and Army Wellness Centers.

The Holistic Health and Fitness program, or H2F, is the framework to encompass all aspects of human performance to include physical, sleep, nutritional, spiritual, and mental fitness, said Maj. Gen. Lonnie G. Hibbard, commander of the U.S. Army Center for Initial Military Training in a press release.

The Department of Veterans Affairs has introduced similar programming aimed at addressing the causes of illness rather than symptoms.

The biggest thing is awareness and education and advocacy, said Dardia. The earlier servicemembers can learn to prevent toxic exposure and recover from stress and sleep deprivation, the healthier theyll be in the long term.

Now the operations sergeant for 3SFGs Human Performance and Wellness program and the Medical Education Transition Advocacy and Assistance program, Dardia is focused on bringing personalized medicine programming to other Special Forces groups, veterans and units across the military.

At Thursdays symposium, Dardia spoke on functional, performance medicine alongside health care professionals from the HunterSeven Foundation.

Members of SOCOMs medical staff attended the three-hour conference in personal capacity, but SOCOM did not officially participate, according to a spokesperson.

Our main focus is research and education, given that we are medical experts with advanced clinical licenses and degrees, said Chelsea Poisson, an Army veteran, emergency nurse and clinical researcher with HunterSeven. The attendees were extremely receptive, I had many questions from members across all communities on resources and what to do next.

In addition to working with members of Congress to give suggestions and solutions to military health care legislature, HunterSeven provides TFDSOF with access to its extensive research on veterans health care issues.

HunterSeven is working on legislation and research to get laws passed that provide our people with better access to health care quicker, said Dardia. Theyre optimizing systems already in place, whether thats in the DoD or at the VA.

As functional, lifestyle-based medicine is adopted across the military, Dardia hopes to work himself out of a job. In years to come, the Green Beret hopes to begin correcting the problem of reactive health care in the civilian population, educating young people about disease prevention and holistic medicine.

We want to advocate this not just for military personnel and veterans; this applies to everybody, said Dardia. This isnt unique to the military. Cancer and suicide are rampant in the civilian population as well, and for the same reasons.

More here:
Personalized medicine is the future of health care for troops, advocates say - Military Times