StemCell Therapy

Researchers at Baylor College of Medicine have discovered a new mechanism that helps maintain and repair bones in adults. Ultimately, this could help develop new therapeutic strategies to improve bone healing.

Knee Bones

Osteoporosis is a skeletal disease characterized by reduced bone density and changes in the microarchitecture of bones. These changes weaken the bone and increase the risk of fractures.

Osteoporosis develops particularly in older people. Today, a new study could eventually lead to the development of therapeutic strategies to improve bone regeneration in these patients. Results published in the journal Cell Stem Cell on the 5th December 2019 have laid out a new mechanism that contributes to the maintenance and repair of bones in adults.

Adult bone repair relies on the activation of bone stem cells, which still remain poorly characterized. Bone stem cells have been found both in the bone marrow inside the bone and also in the periosteum: the outer layer of tissue that envelopes bone. Previous studies have shown that these two populations of stem cells share many characteristics; however, they also have unique functions and specific regulatory mechanisms, said Dr. Dongsu Park, assistant professor of molecular and human genetics, pathology and immunology at Baylor College of Medicine.

Of these two populations, periosteal stem cells are the least known. Although scientists know that this is a heterogeneous population of cells that can contribute to the thickness, formation, and repair of bone fractures, no one has yet been able to distinguish between the different subtypes of bone stem cells in order to study the regulation of their different functions.

Read Also:HGH Is Now A Solid Treatment For Osteoporosis According To Studies

Here, however, Dr. Dongsu Park and colleagues were able to develop a technique in mice to identify different subpopulations of periosteal stem cells, define their contribution to the repair of bone fractures and identify the specific factors that regulate their migration and proliferation under physiological conditions.

The researchers identified a specific subset of stem cells that contribute to lifelong bone regeneration in adults. They also observed that periosteal stem cells react to inflammatory molecules, chemokines, which are normally produced in bone injuries.

In detail, periosteal stem cells have receptors that bind to the CCL5 chemokine. The CCL5 chemokine sends a signal to the cells to migrate to the injured bone and repair it. By suppressing the CCL5 gene in rats, the researchers found defects in bone repair that delayed healing. However, when they gave CCL5 to rats that had lost CCL5, the bones recovered faster.

Read Also:The Exciting Future of Joint and Cartilage Repair

Our findings contribute to a better understanding of the healing of adult bones. We believe this is one of the first studies to show that bone stem cells are heterogeneous and that different subtypes have unique properties that are regulated by specific mechanisms, said Dr. Dongsu Park.

In conclusion, this study has allowed for the identification of different stem cell subtypes and their distinguishing markers and their roles in bone repair. This discovery gives insight into new therapeutic strategies for the treatment of bone damage in adults, particularly in the setting of osteoporosis or diabetes. Indeed, people with diabetes may be prone to falls and fractures due to neurological, visual or renal complications. In addition, bone fragility in diabetics is likely to be due to changes in bone remodeling and, in particular, an increase in bone resorption.

Read Also:Implants from Own Stem Cells May Offer Solution to Back Pain, Researchers Say

https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30458-8?

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Researchers at Baylor College of Medicine Discover How to Improve Bone Repair - Gilmore Health News

Justin Kaus has officiated thousands of basketball games in the last couple of decades, but on Friday night, in the locker room a few minutes before taking the court at Fitzgerald Gym, his resting heart rate was a rapid 118 beats per minute.

Its been a long time since Ive been that nervous and had that much adrenaline for a (junior-varsity) game, Kaus said, gathering with friends later Friday night to celebrate the way basketball officials often do on the weekend. It was awesome.

Kaus returned to the basketball court Friday for the first time since early February, having battled a form of leukemia that halted his professional and athletic career and nearly took his life.

It was great, he said, flexing some stiff muscles and joints. The interaction with coaches, talking with fans, interacting with the players ... you forget how much fun and rewarding that it.

It was more than 14 months since Kaus, 44, went to the clinic, feeling run down and with little energy or strength. He was diagnosed with a sinus infection, but two weeks passed, with stronger antibiotics, and he wasnt feeling any better.

He scheduled a visit to another doctor, who put him through a more extensive examination. He had blood drawn, and, as he was driving home, his doctor called and told him to get to the emergency room.

His hemoglobin level was dangerously low, and Kaus was taken by ambulance to the hospital in Rochester.

I went from thinking I had a sinus infection to having blood cancer in about 6 hours, Kaus said.

Thus began the yearlong process of trying to survive a diagnosis of primary myelofibrosis, a treatable form of leukemia. He continued his normal routine of work and officiating basketball games for a couple of months, trying not to get too worn down.

By February, after finding a couple of perfect donors for a bone-marrow transplant, the treatment became more rigorous and dangerous.

There was a round of chemotherapy in mid-February, followed by a stem cell transplant on Feb. 28. He was told to expect at least 100 days in the hospital, but that time more than doubled when he had to have his spleen removed in March. He developed an infection that required the removal of most of his colon, forcing a lifesaving surgery on May 25.

The doctor told me that if I didnt have my colon removed, it would likely burst, Kaus said. At that point, there would have been nothing more they could do for me.

There were a few weeks during the summer that he cant remember. At one point, he shut off his cell phone after staring at it one day, not sure what he was supposed to do with it. His friends stayed in touch through an online diary, written by his girlfriend, Delight Simpson.

In May, hundreds of Kaus friends gathered for a fundraiser, collecting thousands of dollars to help him with his monthly bills and extra expenses and exchanging hope for Kaus.

I cant thank people enough, he said, getting momentarily choked up with emotion. The support Ive received from my family, my work family, my basketball family has been unbelievable.

Kaus said that since that surgery, his recovery has been rapid and remarkable. Its about what he had originally been told had he not had any complications. Hes had more than 100 blood transfusions, and ironically, he now goes in a couple of times each month to have some blood removed.

After what Ive been through, its hard to watch them just throw that blood away, he said.

He weighed 153 pounds when the treatments began but slipped to 98 pounds. Hes worked hard to get his weight back to near normal, and hes done of lot of rehab work to regain strength. He was unable to lift 2 pounds at his most dire times. He still sees a doctor a couple of times each month, but those visits have become less frequent.

Until recently, he had to rely on Simpson, his daughter, Taylor, and his mom, Sally, to get around, but now hes driving again.

When he started rehab, he couldnt lift 10 pounds on the single-leg press, but hes now up to 125. Hes always been active, participating in sports, and his conditioning has slowly returned.

It felt so good to see him there, said Ben Kaus, Justins cousin and officiating partner on Friday. There was such a shock factor (a year ago) when we found out about his condition, and it took a while to sink in. For a while, we didnt know if Justin was going to be around much longer.

But at one of the visits, when it didnt look very good, he told us that he was going to make it. His positive attitude is what made the difference. Justin has always been like a big brother to me, and its great to have him back.

On Feb. 28, which will be one year from the stem-cell transplant, Kaus will have a checkup to see if the cancer is gone or he needs more treatment. Hell also know shortly after that if he needs to continue with colostomy and ileostomy bags or he can have surgery to reattach his colon to the digestive tract.

Until then, hes going to continue to increase his work hours and officiate basketball as much as his body can tolerate. He wanted to get that first assignment out of the way to see how he felt, then he can plan the next couple of months. Being on the court is as much of a mental triumph as a physical milestone.

In August, I had pretty much written off this season, he said. In early December, it was my 40th physical therapy session in Mankato, my physical therapist suggested that I talk with some coach and go to a scrimmage to simulate basketball movements.

Its the coolest thing to be back on the court, he said. Ive gotten so many messages and words of encouragement and support from the start to this point. This was another step in getting back to normal, and its something Ive worked hard for.

Its never been about me, but the camaraderie being around other officials and telling stories and talking about the games has been very therapeutic. We dont have to (officiate basketball games). We do it because we still enjoy the games and we want to give something back. I hope the coaches, the players, the fans appreciate what we do, but in the end, all that matters is were spending time in the gym, around a game that we love.

Follow Chad Courrier on Twitter @ChadCourrier.

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For Kaus, getting back on court is next step in recovery - Mankato Free Press

Updated January 06, 2020 08:30:20

Since being diagnosed with Hodgkin's lymphoma 18 months ago, Aliona Grytsenko has spent much of her time in and out of hospital.

When the 22-year-old architecture student developed an infection after having a stem cell transplant, she had to be woken every hour to have her vital signs checked.

"It made it really hard to sleep and rest in the midst of having fevers and going through the treatment and side effects themselves. It's really difficult to manage that when you're so sleep-deprived," Ms Grytsenko said.

Registered nurse and researcher Elise Button has worked in cancer and palliative care for 10 years and said waking people up was one of the worst parts of the job.

"We routinely wake people up every four hours if they're more unwell we wake them up every hour or 15 minutes to do vital sign monitoring to make sure they're safe," Dr Button said.

"The sicker they are, the more we wake them up."

But new technology being trialled at the 20-bed Kilcoy Hospital, north-west of Brisbane, may put an end to what has been one of nurses' core responsibilities taking and recording vital signs.

Patients are being fitted with wearable body sensors that will automatically record their temperature, heart rate, oxygen levels and blood pressure.

Dr Button said it was a potential game-changer in nursing care.

"It gives us more time to focus on all the other roles that a nurse does that are important particularly communicating with people, sitting down and talking to them, while we know they're being safely monitored," Dr Button said.

"This allows people who are unwell to get sleep and rest, with peace of mind that they're being safely monitored."

The Metro North Hospital and Health Service's Adam Scott is overseeing the trial and says the feedback so far has been positive.

"Patients have commented they no longer have to be woken through the night. They can sleep through the process," Professor Scott said.

The wireless monitoring technology has been in development for a decade, but it is the first time in the world it has been put to the test by an entire hospital.

It could also help save hospital bottom lines.

"We have a growing level and burden of chronic disease, we have higher life expectancies and higher community expectations on how healthcare is provided," Professor Scott said.

"We know we have to move towards a value-based healthcare approach to better provide services and care for our patients."

The Australian distributor for the wireless monitoring device, Wearable Health Tech, estimates there are more than 100 million patient observations performed each year in Australia.

Company spokesman Ben Magid said the system not only gave time back to staff to spend on patient care, but improved patient safety through continuous monitoring.

"If patients do start to go downhill, staff are alerted so they can intervene sooner and prevent adverse events and complications from developing," Mr Magid said.

If the trial goes well, the technology could be used more widely, allowing patients to recover at home, while still being monitored by hospital staff.

Ms Grytsenko said it would have given her peace of mind.

"In the first few weeks after the stem cell transplant you don't know how you're going, you don't know, is that bad enough that I should call someone and ask or is it OK?'' Ms Grytsenko said.

Professor Scott said he believed it could also revolutionise rural medicine.

"We could have a command centre located in a metropolitan city where the specialist staff are sitting supervising and looking after and viewing patients that are located in a rural facility," Professor Scott said.

The trial will run until June.

Topics:healthcare-facilities,health-policy,health,government-and-politics,public-sector,medical-research,medical-procedures,doctors-and-medical-professionals,brisbane-4000,qld,maroochydore-4558,kilcoy-4515,australia

First posted January 06, 2020 06:56:17

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Wearable monitoring technology helps nurses avoid waking sleep-deprived patients - ABC News

Myelofibrosis or osteomyelofibrosis is a myeloproliferative disorder which is characterized by proliferation of abnormal clone of hematopoietic stem cells. Myelofibrosis is a rare type of chronic leukemia which affects the blood forming function of the bone marrow tissue. National Institute of Health (NIH) has listed it as a rare disease as the prevalence of myelofibrosis in UK is as low as 0.5 cases per 100,000 population. The cause of myelofibrosis is the genetic mutation in bone marrow stem cells. The disorder is found to occur mainly in the people of age 50 or more and shows no symptoms at an early stage. The common symptoms associated with myelofibrosis include weakness, fatigue, anemia, splenomegaly (spleen enlargement) and gout. However, the disease progresses very slowly and 10% of the patients eventually develop acute myeloid leukemia. Treatment options for myelofibrosis are mainly to prevent the complications associated with low blood count and splenomegaly.

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Report Highlights:

The global market for myelofibrosis treatment is expected to grow moderately due to low incidence of a disease. However, increasing incidence of genetic disorders, lifestyle up-gradation and rise in smoking population are the factors which can boost the growth of global myelofibrosis treatment market. The high cost of therapy will the growth of global myelofibrosis treatment market.

The global market for myelofibrosis treatment is segmented on basis of treatment type, end user and geography:

As myelofibrosis is considered as non-curable disease treatment options mainly depend on visible symptoms of a disease. Primary stages of the myelofibrosis are treated with supportive therapies such as chemotherapy and radiation therapy. However, there are serious unmet needs in myelofibrosis treatment market due to lack of disease modifying agents. Approval of JAK1/JAK2 inhibitor Ruxolitinib in 2011 is considered as a breakthrough in myelofibrosis treatment. Stem cell transplantation for the treatment of myelofibrosis also holds tremendous potential for market growth but high cost of therapy is foreseen to limits the growth of the segment.

On the basis of treatment type, the global myelofibrosis treatment market has been segmented into blood transfusion, chemotherapy, androgen therapy and stem cell or bone marrow transplantation. Chemotherapy segment is expected to contribute major share due to easy availability of chemotherapeutic agents. Ruxolitinib is the only chemotherapeutic agent approved by the USFDA specifically for the treatment of myelofibrosis, which will drive the global myelofibrosis treatment market over the forecast period.

Geographically, global myelofibrosis treatment market is segmented into five regions viz. North America, Latin America, Europe, Asia Pacific and Middle East & Africa. Northe America is anticipated to lead the global myelofibrosis treatment market due to comparatively high prevalence of the disease in the region.

Some of the key market players in the global myelofibrosis treatment market are

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The report covers exhaustive analysis on:

Regional analysis includes

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Myelofibrosis Treatment Market To Record Heightened Sales During The Forecast Period 2016 2022 - Market Reports Observer

The idea of transplanting a human head onto another persons body may sound like the stuff of science fiction and thats because it is. But while penning a fictional story about the worlds first cranial exchange, neuroscientist Bruce Mathew came up with an idea that he says could soon become a real-life procedure.

Speaking to The Telegraph, Mathew who was previously the clinical lead for neurosurgery at Hull University Teaching Hospitals NHS Trust explained that a head could be grafted onto another body if the entire spinal cord is transplanted along with it.

Initially our intention was to just brainstorm an idea and it seemed rather silly, but then I realized, it actually isnt. If you transplant the brain and keep the brain and spinal cord together its actually not impossible, he said.

The spinal cord is the most profound thing imaginable. You need to keep the brain connected to the spinal cord. The idea that you cut the spinal cord is utterly ridiculous."

Obviously this is not an easy thing to do, and while recent advances have opened up the possibility of reattaching individual severed nerves, the prospect of connecting an entire spinal column is still some way out of reach.

Yet with surgical technologies improving at a rapid rate, Mathew says it is not entirely unrealistic to think that it will probably happen in the next 10 years.

At the moment, you can connect one or two nerves, but with robotics and artificial intelligence well soon be able to do 200 nerves, he explained.

Of course, there are likely to be many complications with such a procedure, as the recipients body will probably reject such a large amount of donor material. While Mathew hasnt figured out all the solutions in detail, he says that transferring gut bacteria along with the head and spinal cord, and stem cell transplants, may help to ensure that the transplant is accepted.

At present, Mathew has no plans to take his idea any further than the pages of his science fiction novel, although Italian neurosurgeon Sergio Canavero has spent the last few years actively attempting to achieve a human head transplant.

In 2017 he announced that he had successfully transplanted the head of one human corpse onto another, and previously claimed to have grafted a donor head onto a monkey although the animal never regained consciousness and would probably have been paralyzed if it had, as the spinal cord remained unattached.

Despite this, Canavero apparently has a willing human donor, and of course, there are thousands of people (and sometimes just heads) across the world cryonically frozenin the hope medicine and technology of the future will be able to revive them. Perhaps it will happen one day, but we're not quite there yet.

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This Is How Human Head Transplants Could Be Achieved, According To A Neurosurgeon - IFLScience

A former neurosurgeon, who worked with the UKs National Health Service, has a surprising prediction for the next decade. He claims human head transplants will become a reality by 2030.

Dr Bruce Matthew said this during an interview with The Telegraph on December 21. He says the revelation came to him while he was working on a science-fiction novel with futurist author Michal J Lee.

Ifyou transplant the brain and keep the brain and spinal cord together itsactually not impossible. The spinal cord is the most profound thing imaginable.You need to keep the brain connected to the spinal cord. The idea that you cut the spinal cord isutterly ridiculous, he told The Telegraph.

Previous(unsuccessful) attempts at the controversial procedure focused on severing thespinal cord from the brain and then transplanting the head after connectingnerves, blood vessels and meninges (the covering of the brain and spinal cord).

This happened in2017 on a human corpse. Controversial Italian neurosurgeon Dr Sergio Canavero and DrXiaoping Ren of Harbin Medical University, China carried out the 18-hour procedurewhich was later slammed by scientists and bioethicists the world over.

Dr Matthew admits that the future process will be tricky because shifting the spinal cord intact is impossible.

It will take a number of advancements and incremental steps but it will probably happen in the next 10 years, said the former surgeon, who was a clinical lead for neurosurgery at Hull University Teaching Hospitals NHS Trust in the UK and has 25 years of experience.

Hesays the feat will be accomplished with the help of cryogenics (freezing deadbodies in nitrogen), robotics, stem cell therapy and artificial intelligence.

Who will head transplants help?

People with terminal illnesses whose brains are still intact, those with neurodegenerative muscle diseases, the rich who have already frozen their bodies it costs somewhere between $28,000 and $200,000 in hopes of reincarnation.

Basically,those with an intact brain.

Why are head transplants so controversial?

Apartfrom the medical limitations and lack of scientific research on the topic, thebiggest issue that arises is an ethical one.

Doesthe person remain the same person? Will identity also be transferred? DrMatthew says shifting the spinal cord means shifting a persons consciousness. Asfor DNA, hes proposed shifting stem cells from the patient to the donors bodyso a new colony of original DNA can be built.

Scientists also say the donor body runs the risk of being paralysed because of the procedure. Bioethicists say the surgery will have profound psychological, legal and moral complications.

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Transplanting human heads on to another body possible by 2030 - Samaa News

In autologous stem cell and non-stem cell based therapies, an individuals cell is cultured and then re-introduced to the donors body. Used for the treatment of various bone marrow diseases, autologous stem cell and non-stem cell based therapies allows patients to have normal bone marrow, which gets destroyed in chemotherapy. The various diseases that can be treated with the help of autologous stem cell and non-stem cell based therapies include: multiple myeloma, aplastic anemia, non-Hodgkins lymphoma, Parkinsons disease, Hodgkins lymphoma, thalassemia, and diabetes. Thus, the demand for this therapy is projected to rise over the coming years.

The report is a thorough analysis of theAutologous Stem Cell and Non-Stem Cell Based Therapies Market. Comprising an in-depth analysis of the various factors boosting and inhibiting the growth of the market, this report is a key to making profitable decisions by investing in the correct segment and sub-segment, which is anticipated to make the most progress in the future.

Autologous Stem Cell and Non-Stem Cell Based Therapies Market: Trends and Opportunities

One of the key drivers for this market is the rise in the prevalence of cancer and diabetes among people across all age groups. Moreover, the growing geriatric population is another factor, which is likely to create a heightened demand for autologous stem cell and non-stem cell based therapies. Favorable reimbursement policies across several nations are also aiding the growth of this market.

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Players in the market are striving to achieve therapies that are not only safe and effective but also affordable and easy to use. Players are also investing in extensive research and development so as to speed up the treatment process of autologous stem cell and non-stem cell based therapies. While currently this treatment is quite expensive, government bodies are expected to take up initiatives and make the therapy affordable in the years to come. This is expected to drive the market in the future.

On the other hand, challenges faced by the global autologous stem cell and non-stem cell based therapies market include risks and complications associated with the therapy, such as diarrhea, hair loss, nausea, severe infections, vomiting, heart complications, and infertility.

Autologous Stem Cell and Non-Stem Cell Based Therapies Market: Geographical Analysis

By geography, North America, trailed by Europe is leading in the autologous stem cell and non-stem cell based therapies market, on account of the minimization of risks associated with the therapy. Also, these therapies are highly in demand owing to their ability to treat a large number of infectious diseases. The fact that autologous stem cell and non-stem cell based therapies do not require an outside donor, makes it more convenient and less infectious. All these factors are boosting the growth of the market in North America.

Asia Pacific is projected to show the most promising growth in the years to come with high demand from China, Vietnam, Malaysia, and India. The demand is expected to be high as autologous stem cell and non-stem cell based therapies help in the effective treatment of cardiovascular diseases. Sophisticated healthcare infrastructure and favorable tax and reimbursement policies are also expected to aid the growth of the Asia Pacific autologous stem cell and non-stem cell based therapies market.

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Autologous Stem Cell and Non-Stem Cell Based Therapies Market: Companies Mentioned

Some of the leading players operating in the autologous stem cell and non-stem cell based therapies market are Fibrocell Science, Inc., Aastrom Biosciences, Dendreon Corporation, NeoStem, Inc., BrainStorm Cell Therapeutics, Regeneus Ltd., and Genzyme Corporation.

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Autologous Stem Cell and Non Stem Cell Based Therapies Market to Garner Brimming Revenues by 2023 - Industry Mirror

Artificial intelligence tackles life science

Look under the hood of many of this years headline-making discoveries in biology and youll find machine learning, a tool thats gaining ground in the life sciences thanks to growing computational power and the availability of big datasets needed for training. Among other advances in 2019, researchers reported successfully using machine learning to screen images for signs of cancer or infection by pathogens, and to identify epigenetic markers in blood samples that are associated with vascular complications in people with diabetes. Check out our special issue on AI for more examples of how the tool is transforming biology.

Even as computers take on more of the tasks once done by hand, engineers are exploring DNAs capacity to adopt a function usually associated with machines: information storage. This summer, researchers in Boston reported a way of harnessing DNA, together with CRISPR-like base editing machinery, to make a record of events inside living cells that can then be decoded via sequencing. Study coauthor Timothy Lu of MIT told The Scientist that its potential applications include detecting environmental toxins and recording developmental processes.

Another creative spin on CRISPR-Cas9 editing to come out this year is a detection device for particular DNA sequences. Here, the Cas9 enzyme is bound to an RNA and to a graphene chip and engineered not to make cuts in DNA. If the RNA-Cas9 complex connects to its target DNA sequence, it causes a change in the chips electric field and thus a positive readout. The chips developers suggest it could one day be used for quick DNA tests in clinical settings.

Among the endless variations of CRISPR scientists are engineering, one developed this year purports to reduce its off-target effects by avoiding double-strand DNA breaks. The technique, known as prime editing, uses the same Cas9 nuclease as frequently deployed in the CRISPR system but combines the enzyme with a guide RNA called pegRNA and a reverse transcriptase that initiates the addition of a new sequence or base into the genome. Once the new genetic material is incorporated into a cut strand of DNA, the prime editor nicks the unedited strand, signaling to the cell to rebuild it to match the edited strand.

As some researchers worked on their own variations of genome editing, others made an important edit of a recipe for induced pluripotent stem cells. First published by Shinya Yamanaka (now of Kyoto University) in 2006, the method overexpresses genes for four transcription factors in differentiated cells to reset them to a pluripotent state, creating what are known as induced pluripotent stem cells (iPSCs). The most important of the four overproduced factors was thought to be Oct4. But last month, researchers at the Max Planck Institute for Molecular Biomedicine announced theyd not only managed to make mouse iPSCs without tweaking Oct4 levels, but that the process was more efficient that way. If this works in adult human cells, it will be a huge advantage for the clinical applications of iPS cells, Yamanaka wrote in an email to The Scientist.

Shawna Williams is a senior editor atThe Scientist. Email her at swilliams@the-scientist.com or follow her on Twitter @coloradan.

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Top Technical Advances of 2019 - The Scientist

Pike River widow Anna Osborne is "on the up" and out of hospital in time for Christmas.

Osborne, whose husband Milton died in the 2010 Pike River mine disaster, had stem-cell treatment for Hodgkinlymphoma in October.

She had been told she only had a month to a year to live without it.

Phil Walter/Getty

Anna Osborne, from the Pike River Family Reference Group, embraces Prime Minister Jacinda Ardern at the mine entrance earlier this year.

Friend and Pike River mother SonyaRockhouse said Osborne's treatment went well, but there was still a long road ahead.

READ MORE:*Pike River mine tunnel entry an important moment for widow*Pike River re-entry team breaks through into mine drift*Pike River widow 'full of nerves' for mine drift re-entry*The road to getting back into Pike River

"I think the treatment is working for now. She just got her bloods done and they were good and they are the most important thing," she said.

Kevin Stent/Stuff

Osborne and Sonya Rockhouse at the announcement the Government would re-enter the Pike River mine.

Osbornewasdiagnosed with Hodgkinlymphoma in 2002 when she was 36.

She had radiation for six weeks and went into remission, but the cancercame back just before the Pike River tragedy in November 2010, when 29 men where killed in a series of explosions at the coal mine. Osborne helped campaign for thelegalisation of medicinal cannabiswhile undergoing chemotherapy in 2015.

Her stem-cells wereharvested and frozenin August. The stem cell transplanttook place in Christchurch in October aftersix days of intensive chemotherapy.

JOANNE CARROLL/Stuff

Anna Osborne, pictured during treatment for Hodgkins lymphoma in 2016.

The treatment had its own risks.

Osborne was in isolation for five weeks but after shereturned home, she hadsome set backs and small complications,Rockhousesaid.

"She was so crook. She lost a lot of weight. She's had two or three trips to hospital since then," she said.

Supplied/Pike River Recovery Agency

Mine worker Bryan Heslip offers a hand to Osborne and Rockhouse after entering the Pike River mine drift during the re-entry operation.

"She's on the up now,but [there is] still a long way to go. She's at home and is getting some colour back in her cheeks, [and is] starting to look like her old self."

Rockhouse said Osborne was focusing on her recovery and hoped to be able to go to the Pike River mine for the next milestone, which was removing the 170m seal expected to take place in January.

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Pike River widow 'on the up' after stem cell treatment for cancer - Stuff.co.nz

The idea of transplanting a human head onto another persons body may sound like the stuff of science fiction and thats because it is. But while penning a fictional story about the worlds first cranial exchange, neuroscientist Bruce Mathew came up with an idea that he says could soon become a real-life procedure.

Speaking to The Telegraph, Mathew who was previously the clinical lead for neurosurgery at Hull University Teaching Hospitals NHS Trust explained that a head could be grafted onto another body if the entire spinal cord is transplanted along with it.

Initially our intention was to just brainstorm an idea and it seemed rather silly, but then I realized, it actually isnt. If you transplant the brain and keep the brain and spinal cord together its actually not impossible, he said.

The spinal cord is the most profound thing imaginable. You need to keep the brain connected to the spinal cord. The idea that you cut the spinal cord is utterly ridiculous.

Obviously this is not an easy thing to do, and while recent advances have opened up the possibility of reattaching individual severed nerves, the prospect of connecting an entire spinal column is still some way out of reach.

Yet with surgical technologies improving at a rapid rate, Mathew says it is not entirely unrealistic to think that it will probably happen in the next 10 years.

At the moment, you can connect one or two nerves, but with robotics and artificial intelligence well soon be able to do 200 nerves, he explained.

Of course, there are likely to be many complications with such a procedure, as the recipients body will probably reject such a large amount of donor material. While Mathew hasnt figured out all the solutions in detail, he says that transferring gut bacteria along with the head and spinal cord, and stem cell transplants, may help to ensure that the transplant is accepted.

At present, Mathew has no plans to take his idea any further than the pages of his science fiction novel, although Italian neurosurgeon Sergio Canavero has spent the last few years actively attempting to achieve a human head transplant.

In 2017 he announced that he had successfully transplanted the head of one human corpse onto another, and previously claimed to have grafted a donor head onto a monkey although the animal never regained consciousness and would probably have been paralyzed if it had, as the spinal cord remained unattached.

Despite this, Canavero apparently has a willing human donor, and of course, there are thousands of people (and sometimes just heads) across the world cryonically frozenin the hope medicine and technology of the future will be able to revive them. Perhaps it will happen one day, but were not quite there yet.

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This Is How Human Head Transplants Could Be Achieved, According To A Neurosurgeon - Sky Statement

LONDON, Dec. 18, 2019 /PRNewswire/ --GSK today announced positive headline results for intravenous (IV) Benlysta (belimumab) in the largest controlled phase 3 study in active lupus nephritis (LN), an inflammation of the kidneys caused by systemic lupus erythematosus (SLE) which can lead to end-stage kidney disease.

The Efficacy and Safety of Belimumab in Patients with Active Lupus Nephritis (BLISS-LN) study, involving 448 patients, met its primary endpoint demonstrating that a statistically significant greater number of patients achieved Primary Efficacy Renal Response (PERR) over two years when treated with belimumab plus standard therapy compared to placebo plus standard therapy in adults with active LN (43% vs 32%, odds ratio (95% CI) 1.55 (1.04, 2.32), p=0.0311).

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK said: "Lupus nephritis is one of the most common and serious complications of SLE, occurring in up to 60% of adult patients. The results of the BLISS-LN study show that Benlysta could make a clinically meaningful improvement to the lives of these patients who currently have limited treatment options."

Dr Richard Furie,Chief of the Division of Rheumatology and Professor at the Feinstein Institutes atNorthwell Health and Lead Investigator of BLISS-LN said: "My journey with Benlysta began nearly twenty years ago when we performed the very first clinical research trial in lupus patients. To see it culminate in a successful phase 3 lupus nephritis study is a key achievement as the inadequate response of our patients with kidney disease to conventional treatment has long been an area in need of major improvement."

Belimumab also demonstrated statistical significance compared to placebo across all four major secondary endpoints: Complete Renal Response (CRR) after two years (the most stringent measure of renal response), Ordinal Renal Response (ORR) after two years, PERR after one year, and the time to death or renal-related event. In BLISS-LN, safety results for patients treated with belimumab were generally comparable to patients treated with placebo plus standard therapy. The safety results are consistent with the known profile of belimumab.

Benlysta is currently not recommended for use in severe active lupus nephritis anywhere in the world because it has not been previously evaluated in these patients. Based on these positive phase 3 data, GSK plans to progress regulatory submissions in the first half of 2020 to seek an update to the prescribing information.

The full results will be submitted for future presentation at upcoming scientific meetings and in peer-reviewed publications.

About lupus nephritisSystemic lupus erythematosus (SLE), the most common form of lupus, is a chronic, incurable, autoimmune disease associated with a range of symptoms that can fluctuate over time including painful or swollen joints, extreme fatigue, unexplained fever, skin rashes and organ damage. In lupus nephritis (LN), SLE causes kidney inflammation, which can lead to end-stage kidney disease. Despite improvements in both diagnosis and treatment over the last few decades, LN remains an indicator of poor prognosis.1,2 Manifestations of LN include proteinuria, elevations in serum creatinine, and the presence of urinary sediment.

About BLISS-LNBLISS-LN,which enrolled 448 adult patients, was a phase 3, 104-week, randomised, double-blind, placebo-controlled post-approval commitment study to evaluate the efficacy and safety of IV belimumab 10 mg/kg plus standard therapy (mycophenolate mofentil for induction and maintenance, or cyclophosphamide for induction followed by azathioprine for maintenance, plus steroids) compared to placebo plus standard therapy in adult patients with active lupus nephritis. Active lupus nephritis was confirmed by kidney biopsy during screening visit using the 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) criteria, and clinically active kidney disease.

The primary endpoint PERR was defined as estimated Glomerular Filtration Rate (eGFR) 60 mL/min/1.73m2 or no decrease in eGFR from pre-flare of > 20%; and urinary protein:creatinine ratio (uPCR) 0.7; and not a treatment failure. The most stringent secondary endpoint CRR was defined as eGFR is no more than 10% below the pre-flare value or within normal range; and uPCR < 0.5; and not a treatment failure. ORR was defined as complete, partial or no response.

About Benlysta (belimumab)Benlysta, a BLyS-specific inhibitor, is a human monoclonal antibody that binds to soluble BLyS. Benlysta does not bind B cells directly. By binding BLyS, Benlysta inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.

The current US and EU indication for Benlysta are summarised below:

In the US, "Benlysta is indicated for the treatment of patients aged 5 years and older with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. Limitations of Use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Benlysta has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of Benlysta is not recommended in these situations."

Full US prescribing information including Medication Guide is available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Benlysta/pdf/BENLYSTA-PI-MG.PDF

In the EU, "Benlysta is indicated as "add-on therapy in patients aged 5 years and older with active, autoantibody-positive systemic lupus erythematosus (SLE) with a high degree of disease activity (e.g., positive anti-dsDNA and low complement) despite standard therapy."

The Precaution and Warnings for Benlysta includes information that "Benlysta has not been studied in the following adult and paediatric patient groups, and is not recommended: severe active central nervous system lupus; severe active lupus nephritis; HIV; a history of, or current, hepatitis B or C; hypogammaglobulinaenia (IgG < 400mg/dl) or IgA deficiency (IgA < 10 mg/dl); a history of major organ transplant or hematopoietic stem cell/marrow transplant or renal transplant."

The EU Summary of Product Characteristics for Benlysta is available on: http://www.ema.europa.eu

Benlysta is available as an intravenous and a subcutaneous formulation. The Benlysta subcutaneous formulation is not approved for use in children.

GSK's commitment to immunologyGSK is focused on the research and development of medicines for immune-mediated diseases, such as lupus and rheumatoid arthritis, that are responsible for a significant health burden to patients and society. Our world-leading scientists are focusing research on the biology of the immune system with the aim to develop immunological-based medicines that have the potential to alter the course of inflammatory disease. As the only company with a biological treatment approved for adult and paediatric lupus, GSK is leading the way to help patients and their families manage this chronic, inflammatory autoimmune disease. Our aim is to develop transformational medicines that can alter the course of inflammatory disease to help people live their best day, every day.

Important Safety Information for belimumabPlease consult the full Prescribing Information for all the labelled safety information for Benlysta (belimumab)

Contraindications:Previous anaphylaxis with BENLYSTA.

Warnings and precautions: Not recommended in adult and paediatric groups with severe active central nervous system lupus, severe active lupus nephritis, HIV, history of/current hepatitis B or C, hypogammaglobulinaemia (IgG <400 mg/dl) or IgA deficiency (IgA <10 mg/dl) and patients with a history of major organ transplant or hematopoietic stem/cell/marrow transplant or renal transplant.

Mortality:In adult intravenous (IV) clinical trials, death occurred in 0.8% of patients treated with BENLYSTA and in 0.4% of patients receiving placebo; etiologies included infection, cardiovascular disease, and suicide. In the adult SC clinical trial, death occurred in 0.5% of patients receiving BENLYSTA and in 0.7% of patients receiving placebo; infection was the most common cause of death.

Serious Infections:Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including BENLYSTA. The most frequent serious infections in adults treated with BENLYSTA IV included pneumonia, urinary tract infection, cellulitis, and bronchitis. Use caution in patients with severe or chronic infections, and consider interrupting therapy in patients with a new infection.

Progressive Multifocal Leukoencephalopathy (PML):Cases of JC virus-associated PML resulting in neurological deficits, including fatal cases, have been reported in patients with SLE receiving immunosuppressants, including BENLYSTA. If PML is confirmed, consider stopping immunosuppressant therapy, including BENLYSTA.

Hypersensitivity Reactions (Including Anaphylaxis):Acute hypersensitivity reactions, including anaphylaxis (eg, hypotension, angioedema, urticaria or other rash, pruritus, and dyspnea) and death, have been reported, including in patients who have previously tolerated BENLYSTA. Generally, reactions occurred within hours of the infusion but may occur later. Non-acute hypersensitivity reactions (eg, rash, nausea, fatigue, myalgia, headache, and facial edema) typically occurred up to a week after infusion. Patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk. With BENLYSTA SC, systemic hypersensitivity reactions were similar to those in IV trials.

Healthcare providers (HCPs) should monitor patients during and after IV administration and be prepared to manage anaphylaxis; discontinue immediately in the event of a serious reaction. Premedication may mitigate or mask a hypersensitivity response. Advise patients about hypersensitivity symptoms and instruct them to seek immediate medical care if a reaction occurs.

Infusion Reactions:Serious infusion reactions (eg, bradycardia, myalgia, headache, rash, urticaria, and hypotension) were reported in adults. HCPs should monitor patients and manage reactions if they occur. Premedication may mitigate or mask a reaction. If an infusion reaction develops, slow or interrupt the infusion.

Depression and Suicidality:In clinical trials, psychiatric disorders (depression, suicidal ideation and behavior) were reported more frequently in patients receiving BENLYSTA than placebo. In adult trials, psychiatric events reported more frequently with BENLYSTA IV related primarily to depression-related events, insomnia, and anxiety; serious psychiatric events included serious depression and suicidality, including 2 completed suicides. No serious depression-related events or suicides were reported in the BENLYSTA SC trial. Before adding BENLYSTA, physicians should assess patients' risk of depression and suicide and monitor them during treatment. Instruct patients to contact their HCP if they experience new/worsening depression, suicidal thoughts, or other mood changes.

Malignancy:The impact of BENLYSTA on the development of malignancies is unknown; its mechanism of action could increase the risk for malignancies.

Immunization: Live vaccines should not be given for 30 days before or concurrently with BENLYSTA as clinical safety has not been established.

Use With Biologic Therapies or IV Cyclophosphamide:BENLYSTA has not been studied and is not recommended in combination with other biologic therapies, including B-cell targeted therapies, or IV cyclophosphamide.

Adverse Reactions:The most common serious adverse reactions in adults were serious infections: BENLYSTA IV 6.0% (placebo 5.2%), some of which were fatal. Adverse reactions occurring in 3% of adults and 1% more than placebo: nausea 15% (12%); diarrhea 12% (9%); pyrexia 10% (8%); nasopharyngitis 9% (7%); bronchitis 9% (5%); insomnia 7% (5%); pain in extremity 6% (4%); depression 5% (4%); migraine 5% (4%); pharyngitis 5% (3%); cystitis 4% (3%); leukopenia 4% (2%); viral gastroenteritis 3% (1%).

Adverse reactions in pediatric patients aged 5 years receiving BENLYSTA IV were consistent with those observed in adults.

The safety profile observed for BENLYSTA SC in adults was consistent with the known safety profile of BENLYSTA IV with the exception of local injection site reactions.

Pregnancy and lactation:Pregnancy: There are insufficient data in pregnant women to establish whether there is drug-associated risk for major birth defects or miscarriage. After a risk/benefit assessment, if prevention is warranted, women of childbearing potential should use contraception during treatment and for 4 months after the final treatment.

Lactation:No information is available on the presence of belimumab in human milk, the effects on the breastfed infant, or the effects on milk production. Consider developmental and health benefits of breastfeeding with the mother's clinical need for BENLYSTA and any potential adverse effects on the breastfed child or from the underlying maternal condition.

Pediatric Use:The safety and effectiveness have not been established for BENLYSTA IV in patients <5 years of age and for BENLYSTA SC in patients <18 years of age.

Black/African American Patients:In clinical trials there have been mixed results regarding how well BENLYSTA works in this patient population. Consider risks and benefits when prescribing BENLYSTA.

About GSK GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit http://www.gsk.com.

Trademarks are owned by or licensed to the GSK group of companies.

References

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Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2018.

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GSK announces positive headline results in phase 3 study of Benlysta in patients with lupus nephritis - BioSpace

SAN DIEGO, Dec. 12, 2019 /PRNewswire/ -- Aspen Neuroscience, Inc. today announced its launch following a $6.5 million seed round led by Domain Associates and Axon Ventures and including Alexandria Venture Investments,Arch Venture Partners,OrbiMedand Section 32 to develop the first autologous cell therapies for Parkinson's disease. Aspen's proprietary approach was developed by the company's co-founders, Jeanne F. Loring, Ph.D., Professor Emeritus and founding director of the Center for Regenerative Medicine at The Scripps Research Institute, and Andres Bratt-Leal, Ph.D., a former post-doctoral researcher in Dr. Loring's lab. The company was initially supported by Summit for Stem Cell, a founding partner and non-profit organization which provides a variety of services for people with Parkinson's disease. Aspen is led by industry veteran Howard J. Federoff, M.D., Ph.D., as Chief Executive Officer.

Parkinson's disease is characterized by the loss of specific brain cells that make the chemical dopamine. Without dopamine, nerve cells cannot communicate with muscles and people are left with debilitating motor problems. Aspen is focusing on human pluripotent stem cells, cultured cells that can become any cell type in the human body. The company's research is specific to induced pluripotent stem cells (iPSCs), which it develops by taking a skin biopsy from a person with Parkinson's disease and turning the tissue into pluripotent stem cells using genetic engineering. Aspen then differentiates the pluripotent stem cells into dopamine-releasing neurons that can be transplanted into that same person (autologous), thereby restoring the types of neurons lost in Parkinson's disease.

As an autologous cell therapy for Parkinson's disease, Aspen's treatment would eliminate the need for immunosuppression because the neurons are transplanted back into the same patient from which they were generated. The use of immunosuppression is necessary with currently available cell therapies for Parkinson's disease and when transplanting cells from one patient to another (allogeneic) to prevent rejection but can pre-dispose the patient to life-threatening complications including infection and add cost to the patient and health system. Aspen is the only company in the world offering an autologous neuron replacement therapy for Parkinson's disease.

Aspen encompasses a powerful executive leadership team including Dr. Federoff who, in addition to his leadership roles at the UC Irvine Health System, was the Executive Vice President for Health Sciences and the Executive Dean of Medicine at Georgetown University. Dr. Federoff also has significant biotech industry experience including co-founding MedGenesis Therapeutix and Brain Neurotherapy Bio, as well as leading the U.S. Parkinson's Disease Gene Therapy Study Group. The company is also proud to announce the addition of several experienced and well-known members to its leadership team including Edward Wirth, M.D., Ph.D., as Chief Medical Officer.

Dr. Wirth currently serves as the Chief Medical Ofcer for Lineage Cell Therapeutics where he oversees clinical development of its two therapeutic programs for spinal cord injuries and lung cancer. He received his M.D. and Ph.D. from the University of Florida in 1994 and remained to conduct postdoctoral research including leading the University of Florida team that performed the rst human embryonic spinal cord transplant in the U.S. Dr. Wirth went on to serve as the Medical Director for Regenerative Medicine at Geron Corporation where the world's rst clinical trial of human embryonic stem cell (hESC)-derived product occurred which demonstrated initial clinical safety.

Drs. Federoff and Wirth are joined by Dr. Loring, as Chief Scientific Officer; Jay Sial, as Chief Financial Officer; Andres Bratt-Leal, Ph.D., as Vice President of Research and Development; Thorsten Gorba, Ph.D., as Senior Director of Manufacturing and Naveen M. Krishnan, M.D., M.Phil., as Senior Director of Corporate Development.

"Aspen is developing a restorative, disease modifying autologous neuron therapy for people suffering from Parkinson's disease," said Dr. Federoff. "We are fortunate to have such a high-caliber scientific and medical leadership team to make our treatments a reality. Our cell replacement therapy, which originated in the laboratory of Dr. Jeanne Loring and was later supported by Summit for Stem Cell and its President, Ms. Jenifer Raub, has the potential to release dopamine and reconstruct neural networks where no disease-modifying therapies exist."

Aspen's lead product (ANPD001) is currently undergoing investigational new drug (IND)-enabling studies for the treatment of sporadic Parkinson's disease. Aspen is also developing a gene-edited autologous neuron therapy (ANPD002) that is in the research stage and targeted toward familial forms of Parkinson's disease beginning with the most common genetic variant in the gene encoding glucocerebrosidase (GBA). Aspen leverages proprietary machine-learning tools and artificial intelligence to ensure quality control during manufacturing and to deliver a safe and reproducible product for each cell line.

"Aspen's financial backing, combined with its experienced and proven leadership team, positions it well for future success," said Kim P. Kamdar, Ph.D., Partner at Domain Associates, one of Aspen's seed investors. "Domain prides itself on investing in companies that can translate scientific research into innovative medicines and therapies that make a difference in people's lives. We clearly see Aspen as fitting into that category, as it is the only company using a patient's own cells for replacement therapy in Parkinson's disease."

About Aspen Neuroscience

Aspen Neuroscience Inc. is a development stage, private biotechnology company that uses innovative genomic approaches combined with stem cell biology to deliver patient-specific, restorative cell therapies that modify the course of Parkinson's disease. Aspen's therapies are based upon the scientific work of world-renowned stem cell scientist, Dr. Jeanne Loring, who has developed a novel method for autologous neuron replacement. For more information and important updates, please visithttp://www.aspenneuroscience.com.

CONTACT: Jennifer Viera, AspenNeuroscience@TeamSeismic.com

SOURCE Aspen Neuroscience

http://www.aspenneuroscience.com

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Aspen Neuroscience Launches With $6.5 Million Seed Funding to Advance First-of-its-Kind Personalized Cell Therapy for Parkinson's Disease - PRNewswire

Gene therapy is fighting to enter mainstream medicine. With sickle cell disease, the fight is heating up.

Roughly two years ago, the FDA made the historic decision to approve the first gene therapy in the US, finally realizing the therapeutic potential of hacking our biological base code after decades of cycles of hope and despair. Other approvals soon followed, including Luxturna to target inherited blindness and Zolgensma, a single injection that could save children with a degenerative disease from their muscles wasting away and dying before the age of two.

Yet despite their transformative potential, gene therapy has only targeted relatively rareand often fataldisorders. Thats about to change.

This year, a handful of companies deployed gene therapy against sickle-cell anemia, a condition that affects over 20 million people worldwide and 100,000 Americans. With over a dozen therapies in the run, sickle-cell disease could be the indication that allows gene therapy to enter the mainstream. Yet because of its unique nature, sickle-cell could also be the indication that shines an unflinching spotlight on challenges to the nascent breakthrough, both ethically and technologically.

You see, sickle-cell anemia, while being one of the worlds best-known genetic diseases, and one of the best understood, also predominantly affects third-world countries and marginalized people of color in the US. So far, gene therapy has come with a hefty bill exceeding millions; few people afflicted by the condition can carry that amount. The potential treatments are enormously complex, further upping costs to include lengthy hospital stays, and increasing potential side effects. To muddy the waters even more, the disorder, though causing tremendous pain and risk of stroke, already has approved pharmaceutical treatments and isnt necessarily considered life-threatening.

How we handle gene therapies for sickle-cell could inform many other similar therapies to come. With nearly 400 clinical trials in the making and two dozen nearing approval, theres no doubt that hacking our genes will become one of the most transformative medical wonders of the new decade. The question is: will it ever be available for everyone in need?

Even those uninterested in biology have likely heard of the disorder. Sickle-cell anemia holds the crown as the first genetic disorder to be traced to its molecular roots nearly a hundred years ago.

The root of the disorder is a single genetic mutation that drastically changes the structure of the oxygen-carrying protein, beta-globin, in red blood cells. The result is that the cells, rather than forming their usual slick disc-shape, turn into jagged, sickle-shaped daggers that damage blood vessels or block them altogether. The symptoms arent always uniform; rather, they come in crisis episodes during which the pain becomes nearly intolerable.

Kids with sickle-cell disorder usually die before the age of five; those who survive suffer a lifetime of debilitating pain and increased risk of stroke and infection. The symptoms can be managed to a degree with a cocktail of drugsantibiotics, painkillers, and a drug that reduces crisis episodes but ups infection risksand frequent blood transfusions or bone marrow transplants. More recently, the FDA approved a drug that helps prevent sickled-shaped cells from forming clumps in the vessels to further combat the disorder.

To Dr. David Williams at Boston Childrens Hospital in Massachusetts, the availability of these treatmentshowever inadequatesuggests that gene therapy remains too risky for sickle-cell disease. Its not an immediately lethal diseaseit wouldnt be ethical to treat those patients with a highly risky experimental approach, he said to Nature.

Others disagree. Freeing patients from a lifetime of risks and pain seems worthy, regardless of the price tag. Inspired by recent FDA approvals, companies have jumped onto three different treatments in a bitter fight to be the first to win approval.

The complexity of sickle-cell disease also opens the door to competing ideas about how to best treat it.

The most direct approach, backed by Bluebird Bio in Cambridge, Massachusetts, uses a virus to insert a functional copy of the broken beta-globin gene into blood cells. This approach seems to be on track for winning the first FDA approval for the disorder.

The second idea is to add a beneficial oxygen-carrying protein, rather than fixing the broken one. Here, viruses carry gamma-globin, which is a variant mostly present in fetal blood cells, but shuts off production soon after birth. Gamma-globin acts as a repellent that prevents clotting, a main trigger for strokes and other dangerous vascular diseases.

Yet another idea also focuses on gamma-globin, the good guy oxygen-carrier. Here, rather than inserting genes to produce the protein, the key is to remove the breaks that halt its production after birth. Both Bluebird Bio and Sangamo Therapeutics, based in Richmond, California, are pursing this approach. The rise of CRISPR-oriented companies is especially giving the idea new promise, in which CRISPR can theoretically shut off the break without too many side effects.

But there are complications. All three approaches also tap into cell therapy: blood-producing cells are removed from the body through chemotherapy, genetically edited, and re-infused into the bone marrow to reconstruct the entire blood system.

Its a risky, costly, and lengthy solution. Nevertheless, there have already been signs of success in the US. One person in a Bluebird Bio trial remained symptom-free for a year; another, using a CRISPR-based approach, hasnt experienced a crisis in four months since leaving the hospital. For about a year, Bluebird Bio has monitored a dozen treated patients. So far, according to the company, none has reported episodes of severe pain.

Despite these early successes, advocates worry about the actual impact of a genetic approach to sickle-cell disease.

Similar to other gene therapies, the treatment is considered a last-line, hail Mary solution for the most difficult cases of sickle cell disease because of its inherent risks and costly nature. Yet end-of-the-line patients often suffer from kidney, liver, and heart damages that make chemotherapy far too dangerous.

Then theres the problem of global access. Some developing countries, where sickle-cell disease is more prevalent, dont even have consistent access to safe blood transfusions, not to mention the laboratory equipment needed for altering blood-producing stem cells. Recent efforts in education, early screening, and prevention have also allowed people to live longer and reduce the stigma of the disorder.

Is a $1 million price tag ever attainable? To combat exhorbitant costs, Bluebird Bio is offering an installment payment plan for five years, which can be terminated anytime the treatment stops working. Yet for patients in South Africa, India, or Cambodia, the costs far exceed the $3 per month price tag for standard treatment. Even hydroxyurea, the newly-approved FDA drug to reduce crisis pain episodes, is just a fraction of the price tag that comes with gene therapy.

As gene therapy technologies are further refined and their base cost reduced, its possible that overall costs will drop. Yet whether these treatments will be affordable in the long run remains questionable. Even as scientists focus on efficacy rather than price tag, NIH director Dr. Francis Collins believes not thinking about global access is almost unethical. There are historical examples for optimism: vaccines, once rather fringe, now touch almost every corner of our world with the help of scientific knowledge, advocacy groups, andfundamentallyproven efficacy.

With the rise of gene therapy, were now in an age of personalized medicine beyond imagination. Its true that perhaps sickle-cell disease genetic therapies arent quite there yet in terms of safety and efficacy; but without tackling access issues, the therapy will be stymied in its impact for global good. As genetic editing tools become more powerful, gene therapy has the potential to save even more livesif its made accessible to those who need it most.

Image Credit: Image by Narupon Promvichai from Pixabay

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Gene Therapy for Sickle-Cell Anemia Looks Promisingbut It's Riddled With Controversy - Singularity Hub

The ODAC discussions were based on the supplemental Biologics License Application (sBLA), currently under priority review at the FDA, seeking approval of KEYTRUDA monotherapy for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, NMIBC with carcinoma in-situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy (removal of bladder). This application is based on results from the Phase 2 KEYNOTE-057 trial.

The positive vote from todays ODAC meeting supports the potential for KEYTRUDA in certain patients with high-risk, non-muscle invasive bladder cancer, who currently have limited non-surgical treatment options approved by the FDA, said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. We are encouraged by todays productive discussion and look forward to working with the FDA as they continue their review of our supplemental application for KEYTRUDA in this patient population.

The ODAC provides the FDA with independent, expert advice and recommendations on marketed and investigational medicines for use in the treatment of cancer. The FDA is not bound by the committees guidance but takes its advice into consideration. Merck anticipates a Prescription Drug User Fee Act (PDUFA), or target action date, in January 2020, based on priority review.

About Bladder Cancer

Bladder cancer begins when cells in the urinary bladder start to grow uncontrollably. As more cancer cells develop, they can form a tumor and spread to other areas of the body. Bladder cancers are described based on how far they have invaded into the wall of the bladder. NMIBC occurs when the cancer has not grown into the main muscle layer of the bladder. It is estimated that more than 80,000 new cases of bladder cancer will be diagnosed in 2019 in the United States. Approximately 75% of patients with bladder cancer are diagnosed with non-muscle invasive bladder cancer (NMIBC). For high-risk NMIBC patients who are BCG-unresponsive with persistent or recurrent disease, treatment guidelines recommend radical cystectomy, a surgery to remove the entire bladder that often requires removal of other surrounding organs and tissues. In men, removal of the prostate is common, and in women, surgeons may also remove the uterus, fallopian tubes, ovaries and cervix, and occasionally a portion of the vagina.

About KEYNOTE-057

The filing was based on data from KEYNOTE-057 (NCT02625961), a Phase 2, multicenter, open-label, single-arm trial in 102 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 were ineligible for or had elected not to undergo cystectomy (Cohort A). In this study, BCG-unresponsive high-risk NMIBC is defined as persistent disease despite adequate BCG therapy, disease recurrence after an initial tumor-free state following adequate BCG therapy, or T1 disease following a single induction course of BCG. Patients received KEYTRUDA 200 mg every three weeks until unacceptable toxicity, persistent or recurrent high-risk NMIBC or progressive disease. Assessment of tumor status was performed every 12 weeks, and patients without disease progression could be treated for up to 24 months. The major efficacy outcome measures were complete response (as defined by negative results for cystoscopy [with transurethral resection of bladder tumor (TURBT)/biopsies as applicable], urine cytology, and computed tomography urography [CTU] imaging) and duration of response.

About KEYTRUDA (pembrolizumab) Injection, 100mg

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 1,000 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 patients likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications

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.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of 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 confirmatory trials.

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 head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of 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.

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. 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 confirmatory trials. 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 [combined positive score (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.

Microsatellite Instability-High (MSI-H) 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.

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 recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

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).

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes 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.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency), thyroid function (prior to and periodically during treatment), and hyperglycemia. For hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or 4 hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

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 a PD-1 or PD-L1 blocking antibody 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-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

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; 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%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

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.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those 1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those 2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those 2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

Adverse reactions occurring in patients with gastric cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Adverse reactions occurring in patients with esophageal cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

Adverse reactions occurring in patients with hepatocellular carcinoma (HCC) were generally similar to those in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of ascites (8% Grades 34) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 34) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse reactions occurring in patients with MCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. Laboratory abnormalities (Grades 34) that occurred at a higher incidence were elevated AST (11%) and hyperglycemia (19%).

In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

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FDA Oncologic Drugs Advisory Committee (ODAC) Recommends KEYTRUDA (pembrolizumab) for the Treatment of Certain Patients with High-Risk, Non-Muscle...

New technologies that could soon diagnose Alzheimers and restore speech to the paralyzed; potential new avenues in treating diabetes, multiple sclerosis and Down syndrome; and a genetic test that dramatically saved a babys life these were among the science and health topics that most engaged our readers in 2019.

Look back at these 11 stories of the past year or discover them for the first time they reflect the exciting, transformative research that takes place at UC San Francisco every day of the year.

Researchers trained a machine-learning algorithm on nearly 2,000 brain scans and then challenged it to detect early-stage Alzheimers disease in other scans. The algorithm performed with flying colors, catching the disease six years before a clinical diagnosis a lead time that may eventually help doctors treat the disease.

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For California, a 1 percent drop in the smoking rate could mean $630 million of Medicaid savings the following year. Thats because quitting smoking can reduce many health risks relatively quickly, including heart attacks, lung disease and pregnancy complications, as well as cut long-term health risks such as cancer.

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For the first time, researchers were able to transform human stem cells into mature insulin-producing cells similar to the pancreatic beta cells destroyed by type 1 diabetes. The breakthrough came after the team applied a key tenet of biology, that form follows function, to the way they were growing the cells in the lab.

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Researchers took a new approach to studying Down syndrome focusing on the conditions effect on the protein-making machinery inside cells. In a mouse model of Down syndrome, they found that cells in the brain were tamping down on protein production, leading to cognitive deficits. They were able to activate protein production and improve memory and learning with a drug called ISRIB.

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A sophisticated brain-machine interface could one day give voice to people who have lost the ability to speak due to paralysis or other neurological damage. Researchers first mapped participants brain activity to their vocal tract movements as they made various sounds. An algorithm could then translate new brain activity into movements of the virtual vocal tract and produce realistic speech.

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Whats the best way to eat your vegetables? Should you take supplements? Low-fat, low-carb, intermittent fasting do any diets actually work? Experts weigh in on the latest science behind healthy eating and separate food fact from food fiction. Keep these evidence-based tips in mind for the holidays and in the years to come.

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Baby Quincy was deteriorating fast from an aggressive blood cancer and too sick to undergo a stem cell transplant, his only chance at a cure. Determined to leave no stone unturned, Quincys doctors ordered the UCSF500 a new comprehensive cancer gene panel test that helped to reveal an unusual genetic alteration in his cancer and identified a long-shot therapy.

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Multiple sclerosis (MS) is an autoimmune disease caused by immune cells that attack the protective coating around nerve cells. In a surprise, researchers discovered that other immune cells in the gut, known as plasma cells, can reduce the brain inflammation that results from the disease. Expanding these gut plasma cells may be a new therapeutic approach to treating MS.

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Cooking food changes not only how it tastes but how our gut microbial ecosystems respond. In mice, researchers found that cooked vegetables altered their gut microbiome and caused them to lose weight. In human participants, three days of raw or cooked diets prepared by a professional chef also changed gut microbiomes, but in different ways perhaps holding clues to how our microbes have adapted to human culinary culture.

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Alcohol-associated liver disease has become the top reason for U.S. liver transplants, making up more than one-third of liver transplants in 2016. The increase is largely due to a shift away from a common rule that required patients to abstain from alcohol and drug use for at least six months prior to transplant. A 2011 study found that transplants could be successful without this minimum sobriety period, changing the policy at many centers.

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The emotional tumult of teenage years may in part be due to transformations in the brain. Most human brain cells mature in the first years of life, but a group of neurons in the amygdala, which controls emotional responses, dont mature until adolescence and a small number remain immature throughout life. The brain may hold on to these Peter Pan neurons to keep the brains emotional responses flexible and adaptable into old age.

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In 2019, UCSF drove advancements in care delivery, scientific discovery, education, public service, and more. See the highlights

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UCSF's 11 Most Popular Health and Science Stories of 2019 - UCSF News Services

Specializing in innovative cosmetic applications for the face, eyes, and body, Dr. Zamora is a leader in minimally invasive treatments.

DENVER (PRWEB) December 18, 2019

Dr. Jack Zamora, a renowned face expert in Denver, Colorado has joined the esteemed Haute Beauty network.

The Haute Beauty Network, well known for its exclusive and luxurious lifestyle publication Haute Living is privileged to present Dr. Jack Zamora as a face expert and our newest addition to the Haute Beauty members-only network.

Haute Beauty offers a prominent collective of leading doctors. The invitation-only exclusive publication maintains elite as ever, with only two doctors in every market. This partnership allows Haute Beauty to connect its affluent readers with industry-leading aesthetic surgeons located in their area.

ABOUT DR. ZAMORADr. Jack Zamora is an oculofacial plastic surgeon, and a pioneer in plasma treatments and stem cell technology. Specializing in innovative cosmetic applications for the face, eyes, and body, Dr. Zamora is a leader in minimally invasive treatments. Graduating from Tulane University in New Orleans, he received a doctorate degree in medicine and completed his internship at Boston Medical Center (internal medicine), his residency at Boston University (ophthalmology department), and completed his fellowship at Boston University (ophthalmology and oculoplastics).

Dr. Zamora is the medical director of several locations throughout Colorado offering select surgical and non-surgical facial refinement, skin rejuvenation, and body sculpting services. Known for exceptional patient care and state-of-the-art procedures that achieve natural-looking results with as little downtime as possible, Dr. Zamora and his team work with each patient to tailor a combination of treatments for long-term results.

As the creator of J-Plazty, Dr. Zamora has received national and international attention for his revolutionary technique. J-Plazty is a minimally invasive procedure that uses Renuvion plasma energy sub-dermally to instantly tighten and rejuvenate skin anywhere on the face and body without large incisions, downtime, or the complications of traditional surgery. As an authority on skin tightening applications, Dr. Zamora has seen remarkable results with plasma and often combines it with other radiofrequency (RF) modalities for superior rejuvenation. Utilizing his plasma techniques with micro and macro-needling radiofrequency (RF), Dr. Zamora is seeing unparalleled skin shrinkage as well as tightening of extremely delicate tissue allowing for long-term improvement with less downtime

In an effort to improve the outcome of aesthetic procedures, Dr. Zamora has partnered with Vitro BioPharma to develop the worlds first ultra pure cosmetic stem cell serum, InfiniVive MD, to be used topically by plastic surgeons, cosmetic surgeons, and aestheticians throughout the United States. InfiniVive MD is the highest quality cGMP-grade cosmetic stem cell serum containing ultra pure mesenchymal stem cells and exosomes. InfiniVive MD is to be used with ablative and non- ablative lasers, plasma energy technologies, and microneedling radiofrequency. The serum provides an unprecedented improvement in fine lines and wrinkles, helps reduce the signs of aging, and helps promote accelerated healing.

Being an international trainer for J-Plazty, Apyx Medical, and Bausch Health Companies Inc., and a luminary for AMP Medical, Lutronic Medical, and Syneron ELOS, Dr. Zamora offers his expertise to physicians from around the globe. He is a regular speaker and consultant, has been featured on The Doctors TV Show, and has written on the techniques and parameters of soft tissue coagulation and subcutaneous neck skin plasma tightening. Valuing continued education, Dr. Zamora created the Jack Zamora MD Aesthetic Institute, which offers advanced aesthetic training to medical professionals and licensed aestheticians.

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Dr. Jack Zamora Partners with the Exclusive Haute Beauty Network - PR Web

ACLT (THE African Caribbean Leukaemia Trust) has been honoured by blood cancer charity Anthony Nolan, at an awards ceremony held at the Tower of London.

ACLT took home the award for the black, Asian and minority ethnic advocate of the year, in recognition of the work they have done to recruit more donors from these backgrounds to the stem cell register.

The charity is committed to providing hope to patients living with blood cancer and illnesses where a matched donor (stem cell, blood or organ) is required to save a life.

The prestigious Anthony Nolan Supporter Awards were back for their seventh year to recognise the outstanding achievements of the volunteers, fundraisers, and campaigners who help the pioneering blood cancer charity save lives.

Over 23 years, ACLT have recruited thousands of potential donors from African and Caribbean descent to the Anthony Nolan stem cell register, with many people going on to donate to patients in desperate need of a life-saving stem cell transplant.

ACLT was founded IN 1996 by Beverley De Gale OBE and Orin Lewis OBE while they were searching for a matching donor for their 6-year-old son, Daniel.

Daniel had Acute Lymphoblastic Leukaemia and needed a life-saving stem cell transplant, but at the time of his diagnosis in 1993, the number of potential donors on the register from BAME backgrounds was remarkably low. His parents were told Daniel had a 1 in 250,000 change of finding a match.

Beverley and Orin could not sit back and watch this. They got in touch with Anthony Nolan to find out how they could help, and soon after, ACLT was born. From comedy clubs, to churches, to schools, Beverley and Orin organised recruitment events far and wide to reach out to the communities most underrepresented on the stem cell register.

In 1999, Daniel De Gale was the first black person in the UK to receive a stem cell transplant from an unrelated donor. He went on to live a full and busy life, but sadly died from multiple organ failure in 2008, due to complications with his health sustained while waiting for a transplant.

ACLT is Daniels legacy, and his parents have been committed to recruiting donors and raising awareness ever since.

In the last year alone, ACLT have run 13 recruitment events to register potential donors to the Anthony Nolan Stem Cell Register, which have seen over 800 people join. Around 75% of those donors were from BAME backgrounds, and 8 people went on to donate their stem cells to patients in need.

Beverley De Gale OBE said: ACLT have been working in partnership with Anthony Nolan since the charity was formed over 23 years ago. In this time the relationship between ACLT and Anthony Nolan has grown exponentially. Were honoured to have our work of raising awareness and registering lifesaving donors recognised with the prestigious award of BAME Advocate of the Year.

Henny Braund, Chief Executive at Anthony Nolan, said: ACLT is a hugely deserving winner of this award; their incredible support and passion for our work is a fantastic example of our charity, which is built on making lifesaving connections. It was lovely to meet some of ACLTs volunteers at the ceremony and I continue to find myself inspired and humbled by the dedication and strength of supporters like them.

By recruiting potential donors, we are curing blood cancer together. We can give families hope, and give more people a future. But without supporters like ACLT lives cant be saved. Without them, there is no cure.

The awards took place on Thursday 28 November at the Tower of London and were hosted by comedian Nish Kumar.

Anthony Nolan is the charity that finds matching stem cell donors for people with blood cancer and blood disorders and gives them a second chance at life. It also carries out ground-breaking research to save more lives and provide information and support to patients after a stem cell transplant, through its clinical nurse specialists and psychologists, who help guide patients through their recovery.

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ACLT wins National Charity Award - The Voice Online

Nonalcoholic steatohepatitis (NASH) is the most severe form of non-alcoholic fatty liver disease. It is diagnosed by conditions such as a fatty liver, liver cell damage, and inflammation. If it is not treated on time, NASH can lead to further complications such as liver fibrosis. As it is essential to cure NASH in real-time, many companies focus on the same and Promethera Biosciences based in Wallonia, Belgium is one of them.

Take a look at winners of EIT Digital Challenge 2019.

Belgian biotech startup Promethera Biosciences is one of the leading innovators in the world specialised in liver therapeutics. The company operates with the mission to bring life-saving treatments that will reduce the need for liver transplantation. It is one of the pioneers in the development of cell-based therapies that will provide both anti-fibrotic and immunomodulatory effects in the liver.

Promethera Biosciences just announced that it secured 7.5 million additional Series D funding, which adds to the recently raised 39.7 million funding. This investment was led by Sony Innovation Fund of IGV and Pegasus Tech Ventures along with MEDIPAL Holdings, the family office Six Snow, a Japanese private investor and a Belgian private investor.

With the fresh round of investment, Promethera Biosciences aims to advance its clinical programs in NASH (Non-alcoholic steatohepatitis) and ACLF (Acute-on-Chronic Liver Failure). Besides these advancements, the Belgian startup also plans to accelerate growth in the Asian markets. It is in plans to initiate clinical trials outside of Europe in NASH and ACLF in 2020.

Promethera Biosciences lead clinical program is derived from its patented allogenic live-cell platform dubbed HepaStem. The biotech startup has developed its cell therapy technologies using allogeneic stem and progenitor liver cells that are isolated, expanded, and purified from healthy human livers unsuitable for transplantation.

Besides the cell-based therapies, this startup also develops antibody technologies such as the anti TNF-R1 antibody Atrosimab in order to complement and diversify the therapeutic options.

Main image picture credits: Promethera Biosciences

Stay tuned toSilicon Canalsfor more European technology news.

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Promethera Biosciences, a Belgian startup that works on treating liver diseases secures funding - Silicon Canals

Led by researchers at Baylor College of Medicine, a study published in the journal Cell Stem Cell reveals a new mechanism that contributes to adult bone maintenance and repair and opens the possibility of developing therapeutic strategies for improving bone healing.

Adult bone repair relies on the activation of bone stem cells, which still remain poorly characterized, said corresponding author Dr. Dongsu Park, assistant professor of molecular and human genetics and of pathology and immunology at Baylor. Bone stem cells have been found both in the bone marrow inside the bone and also in the periosteum the outer layer of tissue that envelopes the bone. Previous studies have shown that these two populations of stem cells, although they share many characteristics, also have unique functions and specific regulatory mechanisms.

Of the two, periosteum stem cells are the least understood. It is known that they comprise a heterogeneous population of cells that can contribute to bone thickness, shaping and fracture repair, but scientists had not been able to distinguish between different subtypes of bone stem cells to study how their different functions are regulated.

In the current study, Park and his colleagues developed a method to identify different subpopulations of periosteum stem cells, define their contribution to bone fracture repair in live mouse models and identify specific factors that regulate their migration and proliferation under physiological conditions.

Periosteal stem cells are major contributors to bone healing

The researchers discovered specific markers for periosteum stem cells in mouse models. The markers identified a distinct subset of stem cells that contributes to life-long adult bone regeneration.

We also found that periosteum stem cells respond to mechanical injury by engaging in bone healing, Park said. They are important for healing bone fractures in the adult mice and, interestingly, their contribution to bone regeneration is higher than that of bone marrow stem cells.

In addition, the researchers found that periosteal stem cells also respond to inflammatory molecules called chemokines, which are usually produced during bone injury. In particular, they responded to chemokine CCL5.

Periosteal stem cells have receptors molecules on their cell surface that bind to CCL5, which sends a signal to the cells to migrate toward the injured bone and repair it. Deleting the CCL5 gene in mouse models resulted in marked defects in bone repair or delayed healing. When the researchers supplied CCL5 to CCL5-deficient mice, bone healing was accelerated.

The findings suggested potential therapeutic applications. For instance, in individuals with diabetes or osteoporosis in which bone healing is slow and may lead to other complications resulting from limited mobility, accelerating bone healing may reduce hospital stay and improve prognosis.

Our findings contribute to a better understanding of how adult bones heal. We think this is one of the first studies to show that bone stem cells are heterogeneous and that different subtypes have unique properties regulated by specific mechanisms, Park said. We have identified markers that enable us to tell bone stem cell subtypes apart and studied what each subtype contributes to bone health. Understanding how bone stem cell functions are regulated offers the possibility to develop novel therapeutic strategies to treat adult bone injuries.

Reference

Ortinau et al. (2019) Identification of Functionally Distinct Mx1+SMA+ Periosteal Skeletal Stem Cells. Cell Stem Cell. DOI: https://doi.org/10.1016/j.stem.2019.11.003

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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New Mechanism of Bone Maintenance and Repair Discovered - Technology Networks

SAN DIEGO, Dec. 12, 2019 /PRNewswire/ -- Aspen Neuroscience, Inc. today announced its launch following a $6.5 million seed round led by Domain Associates and Axon Ventures and including Alexandria Venture Investments,Arch Venture Partners,OrbiMedand Section 32 to develop the first autologous cell therapies for Parkinson's disease. Aspen's proprietary approach was developed by the company's co-founders, Jeanne F. Loring, Ph.D., Professor Emeritus and founding director of the Center for Regenerative Medicine at The Scripps Research Institute, and Andres Bratt-Leal, Ph.D., a former post-doctoral researcher in Dr. Loring's lab. The company was initially supported by Summit for Stem Cell, a founding partner and non-profit organization which provides a variety of services for people with Parkinson's disease. Aspen is led by industry veteran Howard J. Federoff, M.D., Ph.D., as Chief Executive Officer.

Parkinson's disease is characterized by the loss of specific brain cells that make the chemical dopamine. Without dopamine, nerve cells cannot communicate with muscles and people are left with debilitating motor problems. Aspen is focusing on human pluripotent stem cells, cultured cells that can become any cell type in the human body. The company's research is specific to induced pluripotent stem cells (iPSCs), which it develops by taking a skin biopsy from a person with Parkinson's disease and turning the tissue into pluripotent stem cells using genetic engineering. Aspen then differentiates the pluripotent stem cells into dopamine-releasing neurons that can be transplanted into that same person (autologous), thereby restoring the types of neurons lost in Parkinson's disease.

As an autologous cell therapy for Parkinson's disease, Aspen's treatment would eliminate the need for immunosuppression because the neurons are transplanted back into the same patient from which they were generated. The use of immunosuppression is necessary with currently available cell therapies for Parkinson's disease and when transplanting cells from one patient to another (allogeneic) to prevent rejection but can pre-dispose the patient to life-threatening complications including infection and add cost to the patient and health system. Aspen is the only company in the world offering an autologous neuron replacement therapy for Parkinson's disease.

Aspen encompasses a powerful executive leadership team including Dr. Federoff who, in addition to his leadership roles at the UC Irvine Health System, was the Executive Vice President for Health Sciences and the Executive Dean of Medicine at Georgetown University. Dr. Federoff also has significant biotech industry experience including co-founding MedGenesis Therapeutix and Brain Neurotherapy Bio, as well as leading the U.S. Parkinson's Disease Gene Therapy Study Group. The company is also proud to announce the addition of several experienced and well-known members to its leadership team including Edward Wirth, M.D., Ph.D., as Chief Medical Officer.

Dr. Wirth currently serves as the Chief Medical Ofcer for Lineage Cell Therapeutics where he oversees clinical development of its two therapeutic programs for spinal cord injuries and lung cancer. He received his M.D. and Ph.D. from the University of Florida in 1994 and remained to conduct postdoctoral research including leading the University of Florida team that performed the rst human embryonic spinal cord transplant in the U.S. Dr. Wirth went on to serve as the Medical Director for Regenerative Medicine at Geron Corporation where the world's rst clinical trial of human embryonic stem cell (hESC)-derived product occurred which demonstrated initial clinical safety.

Drs. Federoff and Wirth are joined by Dr. Loring, as Chief Scientific Officer; Jay Sial, as Chief Financial Officer; Andres Bratt-Leal, Ph.D., as Vice President of Research and Development; Thorsten Gorba, Ph.D., as Senior Director of Manufacturing and Naveen M. Krishnan, M.D., M.Phil., as Senior Director of Corporate Development.

"Aspen is developing a restorative, disease modifying autologous neuron therapy for people suffering from Parkinson's disease," said Dr. Federoff. "We are fortunate to have such a high-caliber scientific and medical leadership team to make our treatments a reality. Our cell replacement therapy, which originated in the laboratory of Dr. Jeanne Loring and was later supported by Summit for Stem Cell and its President, Ms. Jenifer Raub, has the potential to release dopamine and reconstruct neural networks where no disease-modifying therapies exist."

Aspen's lead product (ANPD001) is currently undergoing investigational new drug (IND)-enabling studies for the treatment of sporadic Parkinson's disease. Aspen is also developing a gene-edited autologous neuron therapy (ANPD002) that is in the research stage and targeted toward familial forms of Parkinson's disease beginning with the most common genetic variant in the gene encoding glucocerebrosidase (GBA). Aspen leverages proprietary machine-learning tools and artificial intelligence to ensure quality control during manufacturing and to deliver a safe and reproducible product for each cell line.

"Aspen's financial backing, combined with its experienced and proven leadership team, positions it well for future success," said Kim P. Kamdar, Ph.D., Partner at Domain Associates, one of Aspen's seed investors. "Domain prides itself on investing in companies that can translate scientific research into innovative medicines and therapies that make a difference in people's lives. We clearly see Aspen as fitting into that category, as it is the only company using a patient's own cells for replacement therapy in Parkinson's disease."

About Aspen Neuroscience

Aspen Neuroscience Inc. is a development stage, private biotechnology company that uses innovative genomic approaches combined with stem cell biology to deliver patient-specific, restorative cell therapies that modify the course of Parkinson's disease. Aspen's therapies are based upon the scientific work of world-renowned stem cell scientist, Dr. Jeanne Loring, who has developed a novel method for autologous neuron replacement. For more information and important updates, please visithttp://www.aspenneuroscience.com.

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Aspen Neuroscience Launches With $6.5 Million Seed Funding to Advance First-of-its-Kind Personalized Cell Therapy for Parkinson's Disease - P&T...