StemCell Therapy

A spate of new laws goes into effect today following the passage of about 1,200 pieces of legislation by the state legislature during its regular session.

Texans as a whole will be able to text less unless they find themselves in a city like Amarillo where the new state law will trump more restrictive city ordinances and force a more relaxed approach.

That guy walking down the street with a sword wont be subject to arrest.

Jails will follow new mental health procedures and indigent citizens will have new pathways for dealing with minor criminal offenses.

Public safety was at the top of legislators minds during the session that ran from mid-January until the end of May and saw more than 10,000 bills filed for consideration.

Here are a few of the most watched bills that become law today and some insight into how they apply to Amarillo.

Texting and driving (HB 62)

The push for a statewide texting and driving ban has been an ongoing battle for nearly a decade, and this year it was approved by both chambers and signed into law by Gov. Greg Abbott.

The bill bans drivers from texting while a vehicle is moving and makes doing so a misdemeanor offense punishable by a fine of up to $99 on the first offense and up to $200 for repeat offenders. The law only addressees reading, writing or sending electronic messages. So theres going to be a learning curve for police, because certain defenses such as using the phone for a map, for music or for anything other than texting could be used.

Amarillo adopted a hands-free ordinance in September 2012 that was enacted on Jan. 3, 2013. Amarillos local ordinance only allowed drivers to send or view text messages while legally parked, not stopped at a red light, and banned all use of mobile or electronic devices while driving unless they are connected to a hands-free device or for certified emergencies.

The texting and driving law will be uniform for the whole state. This way people can travel from town to town and not have to worry about the laws being different, Amarillo Police Department Office Jeb Hilton said of the new law. The major difference in the state law and the previous city ordinance is that you can now text while stopped at a stop sign or stop light. Our officers will continue to do their best to enforce the law.

Hilton said that from January 1 through July 31, APD wrote 619 citations and issued 244 warnings for use of wireless comunication devices.

While APD will enforce the new law, not everyone associated with the city was happy with the development while it was in special session.

Im really proud of the leadership our city showed five years ago when we enacted that law, Amarillo Mayor Ginger Nelson said of the citys ban on texting and driving. Because this is a public safety issue that will actually decrease the level safety, I am concerned about that.

Large knives (HB 1935)

Its not getting the same chatter as gun laws, but starting next month citizens can openly carry large knives.

State Rep. John Frullo, R-Lubbock, championed a bill that got passed allowing citizens to openly carry large knives in most areas of the state. The bill allows individuals to now carry knives with blades longer than 5 inches, except in certain areas like schools, hospitals and places of worship.

The new knife laws change the wording form illegal knives to location-restricted knives. What this means is that every knife is now legal to carry whether concealed or in the open, Hilton explained. There will still be places that you cannot carry a knife that has a blade that is over 5 inches in length. These include schools, polling places, secure areas of airports, hospitals, churches and bars.

Swords, machetes, Bowie knives and sabers will now be perfectly fine to tote around.

We might see people carrying swords or machetes when the law first goes into effect, but I think once they realize how inconvenient it is things will change, Hilton added. APD wants to stress that there is no reason to call the police just because someone is carrying a large knife or sword in the open, but if they are carrying or using the weapon in a threatening manner be sure to give us a call.

Misdemeanor fines (HB 351)

State lawmakers passed a law aimed at keeping low-income individuals who commit minor offenses out of jail trying to prevent whats often referred to as debtors prisons.

The new law gives judges more leeway in issuing fines and costs for things such as failing to pay parking or speeding tickets, and even the ability to substitute community service for legal fees.

The law aims to make it easier for low-income and low-level offenders to get out of jail, something that local attorneys and prosecutors support with some reservations.

Randall County Distrct Attorney James Farren said he thinks getting low-level and low-income offenders out of jail quickly could help to ease costs by freeing up jail cells, which are a daily expense for taxpayers when occupied. It would also free up space for those who commit the more serious offenses.

Potter County Attorney Scott Brumley agrees with the bills intent but still has some reservations about what costs the city and county might incur.

As I understand, the major impact would be on misdemeanors and non-violent crimes, Brumley said earlier this year when the bill was passed by the House. My reaction I dont oppose looking at the way we improve criminal cases at the pre-trial stage, our office is aware and in agreement, but at some point the county will need a pre-trial services center.

That pre-trial services center or the lack of one in Potter County is one reason Brumley and Farren remain skeptical. The law does not address assisting counties financially to help make pre-trial arrangements for people who could be released early under the bill.

Sandra Bland Act

Lawmakers approved a bill in response to the death of Sandra Bland, who was found dead in a county jail after being held there following a routine traffic stop.

Lawmakers passed a watered-down version of what was originally discussed. The bill that goes into effect Friday mandates that county jails divert people with mental health and substance abuse issues toward treatment and mandates that independent investigations be had if a person dies in custody. The Sandra Bland Act also makes it easier for defendants to receive a personal bond if they have a mental illness or intellectual disability.

Ten other new Texas laws starting today

(HB 25) Eliminates straight-ticket party voting when casting an election ballot.

(HB 29) Allows state lottery winners who win more than $1 million to remain anonymous and prohibits the release of all personal information to the public.

(HB 1424) Prohibits drones and other small aircraft from flying over correction facilities like jails and prisons, and sports venues such as stadiums or facilities with more than 30,000 seats.

(SB 693) Mandates that a school bus be equipped with a three-point seat belt for every passenger. The bill only applies to buses that are 2018-and-newer models.

(SB 16) Reduces the first-time fee for a license to carry from $140 to $40 and the annual renewal fee from $70 to $40.

(HB 810) Allows patients with a severe chronic disease to use stem cell treatment.

(SB 179) Mandates that schools adopt policies related to cyberbullying and requires that schools report offenses. This law also created a new definition of cyberbullying.

(HB 478) If a person enters into a motor vehicle to remove a vulnerable individual, such as a child, that person is immune from civil liability for damage that may occur from entry.

(HB 214) Requires the Supreme Court of Texas and the Court of Criminal Appeals to have audio and video recordings of oral arguments and public meetings available if funds are made available.

(HB 1099) Says landlords cannot prohibit a tenants right to call police or emergency assistance.

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Of cell phones and swords things Amarilloans should know about new state laws - Amarillo.com

The guidelines are expected to have a negative list of around 10 items in which research would be prohibited. Besides, outlining areas in which research is permitted, detailed regulatory and technical guidelines would also be laid out.

Indian Council of Medical Research (ICMR) is set to come out with guidelines for stem cell research in two weeks.

The guidelines are expected to have a negative list of around 10 items in which research would be prohibited. Besides, outlining areas in which research is permitted, detailed regulatory and technical guidelines would also be laid out.

The research wing of ministry of health & family welfare is also going to reduce the time taken for approvals in cord and adult stem cell research.

"These two areas would be decentralized at the institutional level to reduce the bureaucratic hurdles. The ethics committee within each institution can look into it and would be required to report to ICMR," said an ICMR official.

However, for embryonic stem cell research, the National Apex Committee would scan every proposal. "This is so because we want to know how the embryos are procured, what's the procedure etc. This is the area that is most vulnerable to abuse", added the official.

The team of experts are meeting in January-end to finalize the guidelines.

In 2002, draft guidelines were issued that ICMR should be the regulatory authority for biological research and a National Apex Committee for cell-based research & therapy should be set up.

The latter should be vested with powers to examine scientific, technical, ethical, legal and social issues in all the three types of stem cell.

See the article here:
ICMR to release stem cell research guidelines soon - BSI bureau (press release)

About Cellect Biotechnology Ltd.

Cellect Biotechnology is traded the NASDAQ (NASDAQ: "APOP", "APOPW). The Company has developed a breakthrough technology for the isolation of stem cells from any given tissue that aims to improve a variety of stem cells applications.

The Company's technology is expected to provide pharma companies, medical research centers and hospitals with the tools to rapidly isolate stem cells for in quantity and quality that will allow stems cell related treatments and procedures. Cellect's technology is applicable to a wide variety of stem cells related treatments in regenerative medicine and that current clinical trials are aimed at the cancer treatment of bone marrow transplantations.

Forward Looking Statements

This press release contains forward-looking statements about the Company's expectations, beliefs and intentions. Forward-looking statements can be identified by the use of forward-looking words such as "believe", "expect", "intend", "plan", "may", "should", "could", "might", "seek", "target", "will", "project", "forecast", "continue" or "anticipate" or their negatives or variations of these words or other comparable words or by the fact that these statements do not relate strictly to historical matters. For example, forward-looking statements are used in this press release when we discuss the anticipated benefits of a sole listing on Nasdaq. These forward-looking statements and their implications are based on the current expectations of the management of the Company only, and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. In addition, historical results or conclusions from scientific research and clinical studies do not guarantee that future results would suggest similar conclusions or that historical results referred to herein would be interpreted similarly in light of additional research or otherwise. The following factors, among others, could cause actual results to differ materially from those described in the forward-looking statements: changes in technology and market requirements; we may encounter delays or obstacles in launching and/or successfully completing our clinical trials; our products may not be approved by regulatory agencies, our technology may not be validated as we progress further and our methods may not be accepted by the scientific community; we may be unable to retain or attract key employees whose knowledge is essential to the development of our products; unforeseen scientific difficulties may develop with our process; our products may wind up being more expensive than we anticipate; results in the laboratory may not translate to equally good results in real clinical settings; results of preclinical studies may not correlate with the results of human clinical trials; our patents may not be sufficient; our products may harm recipients; changes in legislation; inability to timely develop and introduce new technologies, products and applications, which could cause the actual results or performance of the Company to differ materially from those contemplated in such forward-looking statements. Any forward-looking statement in this press release speaks only as of the date of this press release. The Company undertakes no obligation to publicly update or review any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by any applicable securities laws. More detailed information about the risks and uncertainties affecting the Company is contained under the heading "Risk Factors" in Cellect Biotechnology Ltd.'s Annual Report on Form 20-F for the fiscal year ended December 31, 2016 filed with the U.S. Securities and Exchange Commission, or SEC, which is available on the SEC's website, http://www.sec.gov. and in the Company's period filings with the SEC and the Tel-Aviv Stock Exchange.

ContactCellect Biotechnology Ltd.Eyal Leibovitz, Chief Financial Officerhttp://www.cellect.co+ 972-9-974-1444

SOURCE Cellect Biotechnology Ltd.

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Cellect Shares Will Be Traded From Next Week Exclusively on NASDAQ - PR Newswire (press release)

A new genetics study adds fuel to the debate about muscle aches that have been reported by many people taking popular cholesterol-lowering drugs called statins.

About 60 percent of people of European descent carry a genetic variant that may make them more susceptible to muscle aches in general. But counterintuitively, these people had a lower risk of muscle pain when they took statins compared with placebos, researchers report August 29 in the European Heart Journal.

Millions of people take statins to lower cholesterol and fend off the hardening of arteries. But up to 78 percent of patients stop taking the medicine. One common reason for ceasing the drugs use is side effects, especially muscle pain, says John Guyton, a clinical lipidologist at Duke University School of Medicine.

It has been unclear, however, whether statins are to blame for the pain. In one study, 43 percent of patients who had muscle aches while taking at least one type of statin were also pained by other types of statin (SN: 5/13/17, p. 22). But 37 percent of muscle-ache sufferers in that study had pain not related to statin use. Other clinical trials have found no difference in muscle aches between people taking statins and those not taking the drugs.

The new study hints that genetic factors, especially ones involved in the immune systems maintenance and repair of muscles, may affect peoples reactions to statins. This is a major advance in our understanding about myalgia, or muscle pain, says Guyton, who was not involved in the study.

People with two copies of the common form of the gene LILRB5 tend to have higher-than-usual blood levels of two proteins released by injured muscles, creatine phosphokinase and lactate dehydrogenase. Higher levels of those proteins may predispose people to more aches and pains. In an examination of data from several studies involving white Europeans, people with dual copies of the common variant were nearly twice as likely to have achy muscles while taking statins as people with a less common variant, Moneeza Siddiqui of the University of Dundee School of Medicine in Scotland and colleagues discovered.

But when researchers examined who had pain when taking statins versus placebos, those with two copies of the common variant seemed to be protected from getting statin-associated muscle pain. Why is not clear.

People with double copies of the common form of the gene who experience muscle pain may stop taking statins because they erroneously think the drugs are causing the pain, study coauthor Colin Palmer of the University of Dundee said in a news release.

The less common version of the gene is linked to reduced levels of the muscle-damage proteins, and should protect against myalgia. Yet people with this version of the gene were the ones more likely to develop muscle pain specifically linked to taking statins during the trials.

The finding suggests that when people with the less common variant develop muscle pain while taking statins, the effect really is from the drugs, the researchers say.

But researchers still dont know the nitty-gritty details of how the genetic variants promote or protect against myalgia while on statins. Neither version of the gene guarantees that a patient will develop side effects or that they wont. The team proposes further clinical trials to unravel interactions between the gene and the drugs.

More study is needed before doctors can add the gene to the list of tests patients get, Guyton says. I dont think were ready to put this genetic screen into clinical practice at all, he says. For now, its much easier just to give the patient the statin and see what happens.

More here:
Muscle pain in people on statins may have a genetic link - Science News Magazine

New Delhi [India], Aug 31 (ANI-BusinessWireIndia): PerkinElmer Health Sciences Pvt Ltd (PEHS), a screening and diagnostic laboratory of PerkinElmer, Inc. today announced that it has kicked off a series of seminars for neurologists, paediatricians and gynaecologists in Delhi, Mumbai, Hyderabad, Chennai and Mangalore, India.

These events serve as an ideal platform for discussing PerkinElmers recently launched affordable gene panels, whole exome sequencing (WES) and whole genome sequencing (WGS) services using next generation sequencing and other complementary assays to address the broad range of genetic disorders.

At the first conference, which took place in Delhi, Dr. Madhuri Hegde, Vice President and Chief Scientific Officer, PerkinElmer Diagnostic Laboratory Services, delivered a talk, Simplifying Genomics: Transforming Complexity into Meaning to a group of clinicians.

Starting her presentation, Dr. Hegde said, A growing interest in personalized medicine calls for genome sequencing in clinical diagnostics, but major challenges must be addressed before its full potential can be realized. This talk on a medical genetic testing algorithm will help clinicians select the most appropriate molecular diagnostic tool for each scenario. Dr. Hegde also serves on the board of ACMG Foundation for Genetics and Genomic Medicine and is an Adjunct Professor of Genetics and Paediatrics at Emory University and Georgia Institute of Technology.

Dr. IC Verma, a pioneer in the field of Genetic Medicine joined the session in Delhi and commented: This is a most exciting time in genetics. As a result of the new genomic sequencing technologies, we can arrive at a diagnosis in many more patients than before. Finding the variation in genes is leading to the development of new treatments for the genetic disorders. The medical professionals must take advantage of the genomic tests being offered in India at an affordable rate. The genetic tests enable screening of couples for being carriers of genetic disorders, genetic counseling and prenatal diagnosis to prevent disease and the possibility of new treatments.

Dr. Verma is a renowned medical geneticist. He received genetics training in the UK, USA & Switzerland. He is a Fellow of the Royal College of Physicians, London, the American Academy of Pediatrics, and the National Academy of Medical Sciences, New Delhi. He has received a number of national awards Ranbaxy Science Award, ICMR, NAMS and BC Roy Medical Council award. He is a Member and Vice-chairman of the Ethics Committee of the International Human Genome Organization (HUGO) and serves as an adviser in genetics to the WHO in Geneva, and to Roche Genetics in Basel.

The launch of our genetics service is all about providing quality and specialized service to clinicians in India. Dr. Hegde brings our customers high confidence in PerkinElmers quality sample analysis and reporting, said Jayashree Thacker, President, PerkinElmer India. We have been observing a high demand of sequencing services for rare inherited disease. Combining these offerings with our current portfolio will help address the evolving needs of our customers.

PerkinElmer now offers its customers a global genomic lab testing platform that performs screening and diagnostic testing, specializing in newborn screening and high throughput next generation sequencing for rare inherited diseases. (ANI-BusinessWireIndia)

This is published unedited from the ANI feed.

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PerkinElmer hosts Medical Genomics Seminars in India - India.com

In a step that heralds a new era in cancer treatment, the U.S. Food and Drug Administration said Wednesday it has approved a form of gene therapy that is highly effective at fighting an aggressive form of leukemia in young patients with no other options.

The treatment, to be marketed under the name Kymriah, is neither a pill nor an injection, but a personalized medicine service that functions as a living drug. Patients would have their bodys own disease-fighting T cells fortified and multiplied in a lab, then get the cells back to help them fight their cancer.

In clinical trials of 88 patients with a relapsing or treatment-resistant form of acute lymphoblastic leukemia, 73 went into remission after receiving the experimental treatment.

FDA Commissioner Scott Gottlieb, himself a survivor of blood cancer, predicted that this new approach to cancer treatment will change the face of modern medicine.

Cancer researchers and physicians outside the agency shared Gottliebs enthusiasm.

Dr. Crystal L. Mackall, associate director of Stanford Universitys Cancer Institute, called Kymriah a transformative therapy. It represents an entirely new class of cancer therapies that holds promise for all cancer patients.

Acute lymphoblastic leukemiais the most common form of pediatric cancer, affecting some 3,000 children and young adults yearly in the United States. Though it is considered highly curable in most patients, about 600 each year either do not respond to chemotherapy or see their leukemia return after an initial round of successful treatment.

Those patients dont make it none of them do, said Dr. Stephan A. Grupp, director of the cancer immunotherapy program at Childrens Hospital of Philadelphia, who administered the first course of Kymriah five years ago when it was an experimental treatment called CTL019.

That initial patient, 7-year-old Emily Whitehead of Philipsburg, Pa., saw her leukemia remit completely within three weeks of getting the treatment. Now 12, she was among those calling on the FDA to approve Kymriah for other patients like her.

Certainly for blood cancers, this is a game-changer, Grupp said. Adapting this therapy for patients with solid tumors, he said, will be the work of the next five years.

The new approach was designed to fight some of the most stubborn cancers by giving the bodys immune system a very specific assist.

It starts by harvesting a cancer patients T cells, the warriors of the immune system. The cells are delivered to a specialized lab where scientists alter their DNA, essentially reprogramming them to target cancer cells. These reengineered cells are called chimeric antigen receptor T cells, or CAR-T cells.

The new and improved cells are copied millions of times before theyre sent back to the patient. Once infused into the bloodstream, the CAR-T cells are much better equipped to hunt down and kill cancer cells, wherever they may hide.

Novartis, the company that developed Kymriah, intends to have 32 certified treatment centers up and running by the end of 2018. Patients up to the age of 25 would go to one of these centers to have their T cells harvested and later reintroduced in their modified form.

The cells themselves will be genetically engineered at a Novartis manufacturing facility in Morris Plains, N.J.

Kymriah is the first CAR-T treatment to come before the FDA, but it wont be the last. No fewer than 76 CAR-T treatments are currently under review at the FDA, and Gottlieb predicted that other approvals would follow.

Therapies that would operate in similar ways engineering the immune systems T cells to fight disease more effectively are under investigation for a host of other conditions, including HIV/AIDS, genetic and autoimmune disorders and other forms of cancer.

Todays FDA ruling is a milestone, said Dr. David Maloney, medical director of cellular immunotherapy at Fred Hutchinson Cancer Research Center in Seattle. This is just the first of what will soon be many new immunotherapy-based treatments for a variety of cancers.

Novartis, the Swiss pharmaceutical company that is gearing up to provide Kymriah to as many as 600 patients a year, said it would charge $475,000 for the treatment.

Novartis representatives said they calculated a cost-effective price for the therapy that fell between $600,000 and $750,000. But the company chose instead to charge a price that it said would cover costs, and to introduce a novel approach to billing. Chief Executive Joseph Jimenez said the company will not charge hospitals for the therapy if the patient does not fully respond in a given period of time.

The company also said it will launch a patient assistance program for those who are uninsured or underinsured, and provide some travel assistance for patients and caregivers seeking the treatment.

Gottlieb touted Kymriahs approval as a turning point for the FDA as well. Novartis application for Kymriah came just seven months ago. The agency tagged the application with two designations that ensured its speedy review.

First proposed in 1972, the idea of correcting or enhancing genes to treat disease has a history buoyed by promise but also buffeted by failures. With recent advances in genomic medicine, cell biology and genetic engineering, efforts to locate and edit the genes and cells that play a key role in disease have injected new hope for such treatments.

Gene and cell therapies that target the immune system for enhancement have been particularly promising. They do, however, come with risks specifically, that the activation of immune cells will run amok, sparking reactions ranging from rash and itching to fever and flu-like symptoms that can lead to death.

In approving Kymriah, the FDA warned that it has the potential to cause severe side effects, including cytokine release syndrome, an overreaction to the activation and proliferation of immune cells that causes high fever and flu-like symptoms, and neurological events. Both can be life-threatening. Kymriah can also cause serious infections, low blood pressure, acute kidney injury, fever and low oxygen levels.

The FDA called for continuing safety studies of the new therapy.

melissa.healy@latimes.com

@LATMelissaHealy

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Hailing a breakthrough in fighting cancer, FDA approves gene therapy that functions as a 'living drug' - Los Angeles Times

B. Bick, . Poindexter, UT Med. School/SPL

A depletion of brain cells that produce dopamine is responsible for the mobility problems seen in people with Parkinsons disease.

Japanese researchers report promising results from an experimental therapy for Parkinsons disease that involves implanting neurons made from reprogrammed stem cells into the brain. A trial conducted in monkeys with a version of the disease showed that the treatment improved their symptoms and seemed to be safe, according to a report published on 30 August in Nature1.

The studys key finding that the implanted cells survived in the brain for at least two years without causing any dangerous effects in the body provides a major boost to researchers hopes of testing stem-cell treatments for Parkinsons in humans, say scientists.

Jun Takahashi, a stem-cell scientist at Kyoto University in Japan who led the study, says that his team plans to begin transplanting neurons made from induced pluripotent stem (iPS) cells into people with Parkinsons in clinical trials soon.

The research is also likely to inform several other groups worldwide that are testing different approaches to treating Parkinsons using stem cells, with trials also slated to begin soon.

Nature breaks down the latest research and what it means for the future of stem-cell treatments.

Parkinsons is a neurodegenerative condition caused by the death of cells called dopaminergic neurons, which make a neurotransmitter called dopamine in certain areas of the brain. Because dopamine-producing brain cells are involved in movement, people with the condition experience characteristic tremors and stiff muscles. Current treatments address symptoms of the disease but not the underlying cause.

Researchers have pursued the idea that pluripotent stem cells, which can form any cell type in the body, could replace dead dopamine-making neurons in people with Parkinsons, and thus potentially halt or even reverse disease progression. Embryonic stem cells, derived from human embryos, have this capacity, but they have been the subject of ethical debates. Induced pluripotent stem (iPS) cells, which are made by coaxing adult cells into an emybronic-like state, have the same versatility without the associated ethical concerns.

Takahashis team transformed iPS cells derived from both healthy people and those with Parkinsons into dopamine-producing neurons. They then transplanted these cells into macaque monkeys with a form of the disease induced by a neuron-killing toxin.

The transplanted brain cells survived for at least two years and formed connections with the monkeys brain cells, potentially explaining why the monkeys treated with cells began moving around their cages more frequently.

Crucially, Takahashis team found no sign that the transplanted cells had developed into tumours a key concern with treatments that involve pluripotent cells or that they evoked an immune response that couldnt be controlled with immune-suppressing drugs.

Its addressing a set of critical issues that need to be investigated before one can, with confidence, move to using the cells in humans, says Anders Bjorklund, a neuroscientist at Lund University in Sweden.

I hope we can begin a clinical trial by the end of next year, says Takahashi. Such a trial would be the first iPS cell trial for Parkinson's. In 2014, a Japanese woman in her 70s became the first person to receive cells derived from iPS cells, to treat her macular degeneration.

In theory, iPS cells could be tailor-made for individual patients, which would eliminate the need to use drugs that suppress a possible immune response to foreign tissues.

But customized iPS cells are expensive to make and can take a couple months to derive and grow, Takahashi notes. So his team instead plans to establish iPS cell lines from healthy people and then use immune cell biomarkers to match them to people with Parkinsons in the hope of minimizing the immune response (and therefore the need for drugs to blunt the attack).

In a study described in an accompanying paper in Nature Communications2, Takahashis team implanted into monkeys iPS-cell-derived neurons from different macaques. They found that transplants between monkeys carrying similar white blood cell markers triggered a muted immune reaction.

Earlier this year, Chinese researchers began a Parkinsons trial that used a different approach: giving patients neural-precursor cells made from embryonic stem cells, which are intended to develop into mature dopamine-producing neurons. A year earlier, in a separate trial, patients in Australia received similar cells. But some researchers have expressed concerns that the immature transplanted cells could develop tumour-causing mutations.

Meanwhile, researchers who are part of a Parkinsons stem-cell therapy consortium called GForce-PD, of which Takahashis team is a member, are set to bring still other approaches to the clinic. Teams in the United States, Sweden and the United Kingdom are all planning trials to transplant dopamine-producing neurons made from embryonic stem cells into humans. Previously established lines of embryonic stem cells have the benefit that they are well studied and can be grown in large quantities, and so all trial participants can receive a standardized treatment, notes Bjorklund, also a consortium member.

Jeanne Loring, a stem-cell scientist at the Scripps Research Institute in La Jolla, California, favours transplanting iPS-derived neurons made from a patients own cells. Although expensive, this approach avoids dangerous immunosuppressive drugs, she says. And because iPS cells are established anew for each patient, the lines go through relatively few cell divisions, minimizing the risk that they will develop tumour-causing mutations. Loring hopes to begin her teams trial in 2019. This shouldnt be a race and were cheering for success by all, she says.

Lorenz Studer, a stem-cell scientist at the Memorial Sloan Kettering Cancer Center in New York City who is working on a trial that will use neurons made from embryonic stem cells, says that there are still issues to work out, such as the number of cells needed in each transplant procedure. But he says that the latest study is a sign that we are ready to move forward.

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Reprogrammed cells relieve Parkinson's symptoms in trials - Nature.com

Increased DNA double-strand breaks in Pol-deficient neural progenitors. Credit: Osaka University

DNA is the computer code that programs every event in the body. Despite the importance of DNA fidelity, as the body develops, cells grow and replicate, DNA is constantly turned over. This repeated process can compromise the DNA, so cells have many DNA repair mechanisms. Using mice, Osaka University scientists report a defect in one type of machinery. DNA polymerase (Pol) causes underdevelopment of the brain's cortices and axonal network. The findings could explain cortical development disorders such as autism and microcephaly.

"Pol is responsible for repairing DNA base damage in the brain. Because many neurological disorders are associated with de novo mutations, we wanted to study how loss of Pol affects neuronal development," said Assistant Professor Noriyuki Sugo, an expert in the study of Pol in brain development.

"We found evidence that Pol has a role in the development of the brain but not other organs, and that its defect causes catastrophic DNA double strand breaks (DSBs) and consequent cell death in certain regions of the developing cortex," he said.

These regions represent one of the earliest stages of cortical development, and the generation of cortical neurons is fundamental for proper neural networking.

In the present study, Sugo and his team prepared mutant mice deficient in Pol. These mice showed a large number of DSBs in neural progenitors, the stem cells that eventually produce neurons. Consequently, many immature neurons died through apoptosis. Furthermore, the mice showed defects in the development of specific brain anatomy and the growth of axon in specific cell types, suggesting both an underdevelopment of the cortex and of neural networking.

"We found that Pol deficiency led to higher neuronal cell death in deeper layers than upper layers of the cortex. The deeper layers were thinner," said Sugo. He added that deeper-layer neurons were marked by a higher rate of DSBs.

Neurons formed in these layers are thought essential to the early stages of neural networking. Thus, even if the cells manage to escape death, the brain circuitry is likely compromised.

Finally, proper development depends on both genetic and epigenetic factors. The correction of DNA damage by Pol is an example of genetic regulation. In addition, the researchers found DNA demethylation, an example of epigenetic regulation, is also abnormal in mice deficient of Pol. Together, Sugo argues the findings are strong evidence for the importance of Pol on proper gene expression in cortical development and provide a new target for the study of associated syndromes and disorders.

"The brain is actively constructed in embryonic stages. Neural progenitors produce many neurons, and their genomic DNA is constantly processed. Defects in Pol function could be a new target for explaining cortical developmental disorders."

Explore further: CD38 gene is identified to be important in postnatal development of the cerebral cortex

More information: Kohei Onishi et al, Genome Stability by DNA polymerase in Neural Progenitors Contributes to Neuronal Differentiation in Cortical Development, The Journal of Neuroscience (2017). DOI: 10.1523/JNEUROSCI.0665-17.2017

Excerpt from:
Faulty DNA repair depresses neural development - Medical Xpress

Michael R. Bishop, MD, specializes in the diagnosis and treatment of lymphomas and leukemias. In particular, he cares for patients with hematologic malignancies that have not responded to first-line treatments. An expert in hematopoietic stem cell transplantation (bone marrow transplantation), Dr. Bishop and his team are working to address the unique social, economic, physiological and biological issues that patients face while undergoing this treatment.

His research focuses on the prevention and treatment of relapse after stem cell transplantation. Relapse is the primary cause of treatment failure and death after stem cell transplantation. He has served as the primary investigator on studies designed to prevent and treat disease recurrence after transplantation. Specifically, he works on ways to enhance immune effects of the transplanted cells against cancer.

Bishop has authored more than 150 peer-reviewed articles, in addition to more than 30 book chapters and two books on cancer treatment and research. He also serves on the editorial board of numerous scientific journals, including Biology of Blood and Marrow Transplantation.

He previously served as a senior investigator and as the clinical head of stem cell transplantation for the National Cancer Institute at the National Institutes of Health.

Two of his patients, now in remission, have told their story publicly:

Motivating a Malignant Immune System

The CAR T-cell Chicago story: One year later

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Dr. Bishop @Uchicagomed Knows CAR T-Cell Therapy Backward and Forward - Newswise (press release)

The US Food and Drug Administration indicated Monday that it will be increasing oversight and enforcement to prevent the use of potentially dangerous and unproven stem cell treatments.

The US Food and Drug Administration indicated Monday that it will be increasing oversight and enforcement to prevent the use of potentially dangerous and unproven stem cell treatments.

The US Food and Drug Administration indicated Monday that it will be increasing oversight and enforcement to prevent the use of potentially dangerous and unproven stem cell treatments.

On its website, the agency posted awarning letterthat it sent last week to U.S. Stem Cell Clinic of Sunrise, Florida, accusing the clinic of selling unapproved and nonsterile stem cell treatments and injecting them intravenously or directly into patients spines.

The FDA also said Monday that it sent US marshals last week to StemImmune Inc. of San Diego to seizefive vials of a live virus vaccinereserved for people at high risk of smallpox. After being mixed with stem cells, the unapproved concoction was injected directly into the tumors of cancer patients at California Stem Cell Treatment Centers in Rancho Mirage and Beverly Hills, the FDA said.

Chief Science Officer Kristin Comella of U.S. Stem Cell wrote in astatementthat the company is not violating the law as it is currently written.

It is inappropriate and harmful to state that our clinic is not sterile as we are completely compliant with the regulations for surgical procedures, she wrote. The strict regulations mentioned in the warning letter required to manufacture drugs are not applied to clinics or hospitals.

Comella wrote that the surgical procedure used by the clinic is not subject to the rules for tissue banks which include minimal manipulation and homologous use as described in current federal regulations. She concluded, our clinic is not violating the law as it is currently written.

StemImmune is fully cooperating with the FDA about the development of its stem cell-based investigational cancer therapy, Ulrike Szalay, a spokeswoman for the company, wrote in an email. We look forward to continuing our dialogue with the FDA.

Dr. Elliot B. Lander, co-founder of the California Stem Cell Treatment Center, said it was voluntarily participating in studies for late-stage, no-options cancer patients that had been approved by institutional review boards. The boards are basically bioethics committees, he said, and the one overseeing this study was formed by the International Cell Surgical Society.

We provided our services gratis, for compassionate purposes, and no patient was ever charged, he said. Everything to protect patient safety was done appropriately.

Though the vaccine seized by the FDA falls under the domain of StemImmune, Lander said, we provided autologous stem cells to help carry a viral agent into the cancers. All of the early safety study patient data was submitted in detail to the FDA several months ago. It did show tremendous safety and no adverse events related to the vaccine or cell therapy.

The FDA commissioner, Dr. Scott Gottlieb, issued astatementMonday warning of additional actions in the coming months against a larger pool of actors whose unproven and unsafe products put patients at significant risk.

The International Society for Stem Cell Research commended the FDA for its policy direction and enforcement efforts. President Hans Clevers said the society has been very concerned about reports of patients using unproven stem cell therapies.

Many of these patients have suffered great harm, and even death as a result of using unproven stem cell therapies, Clevers said in a statement. We are hopeful that increased regulatory enforcement against clinics offering unproven treatments will deter this practice and help protect patients.

Ive directed the FDA to launch a new working group to pursue unscrupulous clinics through whatever legally enforceable means are necessary to protect the public health, Gottlieb wrote. We have examples where some of these unproven treatments have clearly harmed patients.

This year, a paper published in the New England Journal of Medicine recounted how three women, ages 72 to 88, with macular degeneration were left blind after a stem cell treatment at an unnamed clinic in Florida in 2015.

I wish it hadnt taken this long, said Leigh Turner, associate professor at the Center for Bioethics at the University of Minnesota. This is a space where the FDA could have taken action four or five years ago as far as making this a policy priority.

Turner said he sees the steps announced Monday as both important and necessary, yet he remains skeptical.

There are important distinctions to be made, and the FDA seems to be making these distinctions in terms of suggesting that they are putting together this working group, a task force, going after businesses marketing unproven interventions, going after businesses making illegitimate or unwarranted claims about stem cell treatment, he said.

Stem cells, like other medical products, generally require FDA approval before they can be marketed. The FDA has not approved any stem cell-based products for use other than cord blood-derived cells, which are blood-forming stem cells, for certain diseases, according to theagencys website.

Gottlieb wrote in his statement its incumbent upon the FDA to make sure the existing legal and regulatory framework is properly defined, with bright lines separating individualized or tailored therapies surgeons are permitted to use from new treatments subject to regulation. Because the field of regenerative medicine is rapidly evolving, he said, close calls may be frequent between what constitutes an individualized treatment and what constitutes an unapproved, possibly harmful medical product.

Turner said Gottliebs statement allowed for a bit of slippage as far as what exactly the FDA is going to do and which businesses they are going to target.

Questions remain as to whether the warning letter is a sign of more letters to come and whether we will see a dramatic increase in such activities from the FDA, Turner said.

FDA spokeswoman Lyndsay Meyer wrote in an email that the agency will seek to take additional actions in the coming months as we address this field, and target those who are clearly stepping over the line.

Yet, Turner asked, what is enough to trigger FDA regulation? Are marketing campaigns and commercial activity enough?

Or do we actually require people being blinded before the FDA does something? he asked, noting that theres a considerable amount of uncertainty in terms of what we should expect in the months ahead. The statement itself doesnt provide clear answers to all those questions.

Susan L. Solomon, CEO of the New York Stem Cell Foundation, a nonprofit research organization, said via a spokesman that the regulation of these clinics is very difficult, so the announcement today that the FDA will be stepping up their oversight should be welcomed and applauded.

Overall, Turner said, the agencys actions should not give all stem cell treatments or doctors performing these regenerative therapies a bad name. There are already effective treatments. If we think about bone transplants as stem cell transplants, its standard of care for certain diseases, he said.

Solomon agreed: There are extremely promising studies and research using stem cells to treat macular degeneration, multiple sclerosis, diabetes and many other devastating diseases. I cannot emphasize enough how exciting and promising the research is.

However, anyone advertising a cure today is simply taking advantage of patients for their own financial gain, she said.

Turner acknowledges the difficulty for patients, who may not easily recognize which stem cell therapies are approved and beneficial and which are not.

If you see a business thats making all sorts of dramatic marketing claims across disease categories, claiming to use fat as a treatment for all sorts of indications, these are all signs to be wary of, he said.

The FDA offersadvice for consumers, Meyer noted, adding that anyone who exploits and deceives patients puts the entire field at risk.

Turner acknowledged stem cell treatments as a very promising area of research, and over time, he expects to see more FDA-approved therapies in the marketplace. The problem, he said, is that many American businesses making claims about stem cell treatments lack proper scientific safety and efficacy data.

Why, for example, didnt California Stem Cell Treatment Centers get a warning letter for all the other treatments they are doing? It leaves me a bit perplexed, he said. Why is the FDA so focused on these vials and not on the broader array of marketing claims that California Stem Cells was making?

Solomon said that by providing unproven treatments to chronically ill or injured patients, these clinics are not only taking advantage of patients, they are muddying the scientific waters of clinical trials that are trying to show whether a treatment does or does not work.

In its statements Monday, the FDA notes the handful of bad actors in the stem cell space, Turner observed. (Meyer repeated the FDAs assertion that its only a small number of unscrupulous actors who have seized on the clinical promise of regenerative medicine.)

Whereas I look and I see hundreds of companies, said Turner, who published apaperon the practice.

Ultimately, Turner is glad for the FDAs actions.

I hope this is a sign that the FDA is going to do a lot more and better regulate this market space so well see whether or not that happens, he said. Its easy to make these bold announcements. The question is going to be whether anything really comes of it.

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FDA cracks down on stem cell clinics | WPMT FOX43 - FOX43.com

Opening a new era in cancer care, the Food and Drug Administration on Wednesday approved the first treatment that genetically engineers patients' own blood cells into an army of assassins to seek out and destroy childhood leukemia.

The CAR-T cell treatment developed by Novartis Pharmaceuticals Corp. and the University of Pennsylvania is the first type of gene therapy to hit the U.S. market and one in a powerful but expensive wave of custom-made living drugs being tested against blood cancers and some tumors.

FDA called the approval historic.

This is a brand new way of treating cancer, said Dr. Stephan Grupp of Children's Hospital of Philadelphia, who treated the first child with CAR-T cell therapy, a girl who had been near death but now has been cancer-free for five years. That's enormously exciting.

CAR-T treatment uses gene therapy techniques not to fix disease-causing genes but to turbocharge T cells, immune system soldiers that cancer too often can evade. Researchers filter those cells from a patient's blood, reprogram them to harbor a chimeric antigen receptor that zeroes in on cancer, and grow hundreds of millions of copies. Returned to the patient, the revved-up cells can continue multiplying to fight disease for months or years.

Novartis said it would charge $475,000 for the treatment, made from scratch for every patient. But the company said there would be no charge if the patient didn't show a response within a month.

We're entering a new frontier in medical innovation with the ability to reprogram a patient's own cells to attack a deadly cancer, FDA Commissioner Scott Gottlieb said.

This first use of CAR-T therapy is aimed at patients desperately ill with a common pediatric cancer acute lymphoblastic leukemia that strikes more than 3,000 children and young adults in the U.S. each year. While most survive, about 15% relapse despite today's best treatments, and their prognosis is bleak.

In a key study of 63 advanced patients, 83% went into remission. It's not clear how long that benefit lasts: Some patients did relapse months later. The others still are being tracked to see how they fare in the long term.

Still, a far higher percentage of patients go into remission with this therapy than anything else we've seen to date with relapsed leukemia, said Dr. Ted Laetsch of the University of Texas Southwestern Medical Center, one of the study sites. I wouldn't say we know for sure how many will be cured yet by this therapy. There certainly is a hope that some will be.

Most patients suffered side effects that can be grueling, even life-threatening. An immune overreaction called cytokine release syndrome can trigger high fevers, causing plummeting blood pressure and, in severe cases, organ damage, requiring special care to tamp down those symptoms without blocking the cancer attack. Also Wednesday, the FDA designated a treatment for those side effects.

The new CAR-T therapy might replace bone marrow transplants that cost more than half a million dollars, said Grupp, who led the Novartis study.

I don't want to be an apologist for high drug prices in the U.S., Grupp stressed. But if it's the last treatment they need, that's a really significant one-time investment in their wellness, especially in kids who have a whole lifetime ahead of them.

Initially, Novartis' CAR-T version to be sold under the brand name Kymriah will be available only through certain medical centers specially trained to handle the sophisticated therapy and its side effects. Patients' collected immune cells will be frozen and shipped to a Novartis factory in New Jersey that creates each dose, a process the company says should take about three weeks.

While this first use of CAR-T therapy only is aimed at a few hundred U.S. patients a year, it's being tested as a treatment for thousands more.

Kite Pharma Inc.'s similar CAR-T brand, developed by the National Cancer Institute, is expected to win approval later this year to treat aggressive lymphoma, and Juno Therapeutics and other companies are studying their own versions against blood cancers including multiple myeloma.

On Monday, Gilead Sciences Inc. announced that it was buying Santa Monica-based Kite in an $11.9-billion deal.

Analysts said the eventual pricing of the Novartis treatment could be an advantage for Kite.

Since these therapies are unbelievably effective for leukemia, Novartis pricing power is high, said Thomas Shrader, biotechnology analyst at Stifel. That means Kite could piggyback off Novartis price, even though its therapy is aimed at non-Hodgkins lymphoma, which has a lower response rate to the therapy than leukemia does.

Scientists around the country also are trying to make CAR-T therapies that could fight more common solid tumors such as brain, breast or pancreatic cancers a harder next step.

Times staff writer Samantha Masunaga contributed to this report.

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UPDATES:

9:55 a.m.: This article was updated with the price of Novartis therapy.

9:45 a.m.: This article was updated with comments from medical experts and a financial analyst, as well as more details about CAR-T therapy.

This article was originally published at 8:25 a.m.

More:
FDA approves historic 'living drug' treatment to fight childhood leukemia - Los Angeles Times

Nanoparticles (orange) deliver temporary gene therapy to immune cells (blue) to give them disease-fighting tools. (Fred Hutch Illustration / Kimberly Carney)

CAR T immunotherapies are all the rage in the medical community, reprogramming a patients immune system to fight cancer. For some patients, theyve produced near-miraculous recoveries, and they could be a huge breakthrough in cancer treatment.

The business community is taking note as well: Kite Pharma, a biotech company developing these therapies, announced a deal to be acquired for $11.9 billion on Monday, sending stock prices of Seattle immunotherapy developer Juno Therapeuticsskyrocketing.

But there are still giant pitfalls to using the therapies on a large scale because they are incredibly complex and expensive to produce. Researchers from Seattles Fred Hutchinson Cancer Research Center are taking the problem head-on with new hit-and-run gene editing technology.

In a study published Wednesday in the journal Nature Communications, researchers led by Dr.Matthias Stephan reported they have developed a nanoparticle delivery system that can temporarily alter cells so they are able to fight cancer and other diseases.

The best part? The treatment is a powder that just needs to be mixed with water to activate and even better, it could be an essential breakthrough in making cutting-edge medical technology affordable for patients.

Stephan told GeekWire in a previous piece on the technology that his goal is to make immunotherapy so easy to access that it replaces chemotherapy as the front-line treatment for cancer.

What I envision is like the Walgreens flu shot scenario, or you go to your doctor and you get hepatitis B shot, he said at the time. You go there every Friday, and thats it.

We realized in order to outcompete chemotherapy, we have to design something that is at least as affordable and can be manufactured at large scale by one biotech company and shipped out to local infusion centers, Stephan said. At the moment, CAR T cell therapies must be made individually for each patient in specialized labs.

Heres how the new tech works: The nanoparticles designed by Stephan and his team act like shipping containers for bundles of mRNA, the molecules that tell cells how to build disease-fighting proteins. The nanoparticles also have molecules attached to the outside to help them find the right kind of cells, like a shipping label on a package.

When the mRNA is delivered to the cell, it prompts the cell to grow disease-fighting features, like the chimeric antigen receptor in CAR T cells that help them identify and kill cancer.Researchers said the technology could potentially be used to develop treatments for HIV, diabetes and other immune-related diseases.

In the short run, the tech could help researchers discover new treatments and therapies in the lab. It could one day be used in hospitals and clinics around the world, but will first need to undergo extensive clinical trials to ensure the tech is effective and safe to use in humans.

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New 'hit-and-run' gene editing tool temporarily rewrites genetics to treat cancer and HIV - GeekWire

31 August 2017 08:22

Almost all men over 60 and women over 75 are eligible for statins

A common genetic variant could be the reason some people suffer from aches and pains when taking statins, according to new research.

The study could lead to a screening method to help identify those patients who are most likely to have a bad reaction to the drugs.

Statin intolerance doubles

Millions of Britons take statins every year to lower cholesterol and reduce their risk of heart attacks and strokes. However, between 7% and 29% of users suffer from sore muscle symptoms, which can in some cases stop them using the pills.

Research undertaken at the University of Dundee found that statin intolerance was doubled when patients carried two identical copies of a common variant of the LILRB5 gene, which has an immune system and muscle repair role.

The team also confirmed that some people are genetically more likely to suffer from aching muscles regardless of whether they are taking statins.

Lead scientist Professor Colin Palmer said: "We found that there are people in the general population who carry a genetic factor that predisposes them to muscle aches. If these people are put on statins, they might discontinue their medication in the erroneous belief that it is the statin that is making their muscles ache."

Sub-group of patients

He added that the researchers also identified a genetic sub-group of patients who are susceptible to statin-specific muscle ache, however, at this stage the reason for this is not understood.

Professor Palmer suggested that in the future prospective statin users could be tested for key genetic variants, including LILRB5.

Almost 12,000 statin users took part in the Genetics of Diabetes Audit and Research Tayside Scotland (GoDARTS) study. The findings will appear in the European Heart Journal.

People with long-term, pre-existing conditions can arrange medical travel insurance should they need to travel.

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Genetics could be behind statin side effects - World First Travel Insurance

Spinal injuries are oftenpermanent, but new research suggests such injuries may be healed, at least in part.Researchers were able to stimulate limb function in paralyzed mice by implanting human stem cells into theirspinal cords. We're not close to repeating the test in people, but the study shows it may be possible some day with further research.

The University of California-San Diego team grafted human neural stem cells (NSCs) into the spinal cord injuries of mice who were purposely injuredto impair the use of their front legs. The stem cells grew slowly, yet steadily, over the course of 18 months, retaining their original function despite being in a strange and challenging environment for an extended period of time. Whats more, eventually the rodents were able to use their front legs again.

"The bottom line is that clinical outcome measures for future trials need to be focused on long time points after grafting," said study researcher Mark Tuszynskiin a recent statement. Relying on shorter time frames might produce misleadingly negative results considering how long it takes neural stem cells to develop, he added.

For the study, the team used H9 human NSCs, which are a type of stem cell derived from human embryonic stem cells, as commonly used in scientific research, the statement reported. They then grafted these human stem cells into the spinal injuries of mice. The researchers observed the rodents recovery over the course of 18 months, noting that significant cellgrowth did occur soon after grafting, and continued up to a year after the initial implantation.

The most important observation was that these cells were able to continue to do what they were designed to doregrow neural cellsdespite the fact that they were transplanted into an entirely different species. This suggests the cells have resilience and similar experiments mayalso work in human subjects.

Before you get too excited about these results, the researchers emphasized that there were a number of caveats. First, humans and mice are entirely different species, and though the results observed in the rodents are promising, we don't know if they could be repeated in people.

Also, the researchers observed that some astrocytes, star-shaped neural cells associated with electrical impulse transmission, did migrate from the original implantation site to other areas of the rodents. These brain cells are classified as glial cells, which are noted to lead to devastating and difficult to treat cancers when they are dysregulated, Harvard University reported. However, there were no tumors or abnormal growths observed in the mice in the study and the researchers are trying to figure out way to make sure cancer doesn't develop.

Ultimately, the team believe that these results stand as a good foundation on which to buildfurther research.

Success, it would seem, will take time," concluded Tuszynski.

Source: Lu P, Ceto S, Wang Y, et al. Prolonged human neural stem cell maturation supports recovery in injured rodent CNS. The Journal of Clinical Investigation . 2017

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Stem Cell Graft Repairs Spinal Cord Injury, Helps Paralyzed Mice Move Again - Medical Daily

AsianScientist (Aug. 30, 2017) - In a study published in Cell Stem Cell, scientists in Japan and Switzerland have found that bacterial infections can stress blood-producing stem cells in the bone marrow and reduce their ability to self-replicate.

When a person becomes infected with a virus or bacteria, immune cells in the blood or lymph react to the infection. Some of these immune cells use sensors on their surfaces, called Toll-like receptors (TLR), to distinguish invading pathogens from molecules that are expressed by the host. By doing so, they can attack and ultimately destroy pathogens thereby protecting the body without attacking host cells.

Bone marrow contains hematopoietic stem cells which create blood cells, such as lymphocytes and erythrocytes, throughout the lifetime of an individual. When infection occurs, a large number of immune cells are activated and consumed. Hence, it is necessary to replenish these immune cells by increasing blood production in bone marrow.

Recent studies have revealed that immune cells are not the only cells that detect the danger signals associated with infection. Hematopoietic stem cells also identify these signals and use them to adjust blood production. However, little was known about how hematopoietic stem cells respond to bacterial infection or how it affected their function.

In this study, researchers from Kumamoto University and the University of Zurich analyzed the role of TLRs in hematopoietic stem cells upon bacterial infection, given that both immune cells and hematopoietic stem cells have TLRs.

To generate a model of bacterial infection, researchers injected one of the key molecules found in the outer membrane of gram negative bacteria and known to cause sepsislipopolysaccharide (LPS)into lab mice. They then analyzed the detailed role of TLRs in hematopoietic stem cell regulation by combining genetically modified animals that do not have TLR and related molecules, or agents that inhibit these molecules.

The results showed that LPS spread throughout the body, with some eventually reaching the bone marrow. This stimulated the TLRs of the hematopoietic stem cells and induced them to proliferate. They also discovered that while LPS promoted stem cell proliferation, it also induced stressed the stem cells, impairing their ability to successfully self-replicate and resulting in diminished blood production. Similar results were obtained after infection with Escherichia coli bacteria.

Fortunately we were able to confirm that this molecular reaction can be inhibited by drugs, said Professor Hitoshi Takizawa of Kumamoto University who led the study. The medication maintains the production of blood and immune cells without weakening the immune reaction against pathogenic bacteria. It might be possible to simultaneously prevent blood diseases and many bacterial infections in the future.

The article can be found at: Takizawa et al. (2017) Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness.

Source: Kumamoto University.Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Originally posted here:
Bacterial Infection Stresses Blood Stem Cells - Asian Scientist Magazine

Gene therapy is the use of DNA as a potential therapy to treat a disease.In many disorders, particularly genetic diseases caused by a single genetic defect, gene therapy aims to treat a disease by delivering the correct copy of DNA into a patients cells.The healthy, functional copy of the therapeutic gene then helps the cell function correctly.

In gene therapy, DNA that encodes a therapeutic protein is packaged within a vector, often a naked virus, which is used to transfer the DNA to the inside of cells within the body. Gene therapy can be delivered by a direct injection, either intravenously (IV) or directly into a specific tissue in the body, where it is taken up by individual cells. Once inside cells, the correct DNA becomes expressed by the cell machinery, resulting in the production of therapeutic protein, which in turn treats the patients disease and can provide long-term benefit.

Abeona is developing next generation adeno-associated virus (AAV) gene therapies. Viruses such as AAV are utilized because they have evolved a way of encapsulating and delivering one or more genes of the size needed for clinical application, and can be purified in large quantities at high concentration. Unlike AAV vectors found in nature, the AAV vectors used by Abeona have been genetically-modified such that they do not replicate. Although the preclinical studies in animal models of disease demonstrate the promising impact of AAV-mediated gene expression to affected tissues such as the heart, liver and muscle, our programs use a specific virus that is capable of delivering therapeutic DNA across the blood brain barrier and into the central nervous system (CNS), making them attractive for addressing lysosomal storage diseases which have severe CNS manifestations of the disease.

Lysosomal storage diseases (LSD) are a group of rare inborn errors of metabolism resulting from deficiency in normal lysosomal function. These diseases are characterized by progressive accumulation of storage material within the lysosomes of affected cells, ultimately leading to cellular dysfunction. Multiple tissues ranging from musculoskeletal and visceral to tissues of the central nervous system are typically involved in disease pathology.

Since the advent of enzyme replacement therapy (ERT) to manage some LSDs, general clinical outcomes have significantly improved; however, treatment with infused protein is lifelong and continued disease progression is still evident in patients. Thus, viral gene therapy may provide a viable alternative or adjunctive therapy to current management strategies for LSDs.

Our initial programs are focused on LSDs such as Mucopolysaccharidosis (MPS) IIIA and IIIB, also known as Sanfilippo syndromes type A and type B. MPS III is a progressive neuromuscular disease with profound CNS involvement. Our lead product candidates, ABO-101 and ABO-102, have been developed to replace the damaged, malfunctioning enzymes within target cells with the normal, functioning version.

Delivered via a single injection, the drug is only given once.

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Gene Therapy - Abeona Therapeutics

Personalized cancer treatments known as CAR-T cells (chimeric antigen receptor T cells) have dominated the headlines lately, thanks to Novartis tisagenlecleucel, which won an early approval from the FDA for the treatment of leukemia on Aug. 30. But CAR-T treatments are labor-intensive and expensive to make, and they can attack healthy tissues in the body, leading to dangerous side effects.

Scientists at the Fred Hutchinson Cancer Research Center have developed a tool that they believe could address both those shortcomings of CAR-T and other forms of cell engineering. They have invented nanoparticles that deliver proteins to cells, which in turn edit those cells genes temporarily. Lead author and bioengineer Matthias Stephan describes it as hit-and-run gene therapy, and he believes the technique will streamline the manufacturing of cell-based therapies.

Heres how it works: The nanoparticles home in on specific cells, such as the T cells in the immune system. They then deposit messenger RNA (mRNA) to those cells, which triggers short-term changes in the proteins the genes produce. The technology does not permanently change the DNA, but it makes enough of an impact on it to produce a therapeutic outcome.

RELATED: Can CAR-T cancer treatments be fine-tuned to avoid toxic side effects?

Whats more, the nanoparticles can be freeze-dried and then activated with a small amount of water. They really let you fulfill all your wishes as a genetic engineer because you can pack in all your different [gene-therapy] components and further improve the therapeutic potential of your cell product without additional manufacturing steps, Stephan said in an article posted on Fred Hutchs website.

Stephans team proved out their concept by testing the nanoparticles in three different cell-engineering applications, one of which was CAR-T. Currently, CAR-T treatments are made by giving T cellsgenes that teach them to destroy cancer cells. The Fred Hutch scientists used their nanoparticles to remove a different gene from T cellsone that normally prompts them to attack healthy tissue.

Then they tried enhancing the CAR-T cells in a different manner. They temporarily gave them genes that have the potential to make central memory T cells, which are able to survive over the long term, remembering their cancerous targets and attacking them should they ever resurface.

The scientists tested their engineered CAR-T cells in mouse models of leukemia and found that the animals that received them lived twice as long as mice that got conventional CAR-T cells. They also tested the nanoparticles in two other cancer-related applications of gene therapy.

Despite all the excitement over CAR-T, concerns about side effects continue to dog the field. A dangerous immune reaction known as a cytokine storm has been seen in trials of both Novartis treatment and Axi-Cel, a CAR-T from Kite Pharma, which is being acquired by Gilead. The third player in the CAR-T field, Juno Therapeutics, saw its late-stage trials delayed when some patients died of neurological side effects.

Fred Hutch scientists have been working on other techniques for improving CAR-T. In December, a set of researchers there who receive funding from Juno announced positive results from a trial of a fine-tuned CAR-T treatment in patients with chronic lymphocytic leukemia (CLL). Instead of using just one type of CAR-T, the team combined two specially selected cell subtypes into one treatment. They also announced they had identified biomarkers that they believe can be used to predict which patients are likely to have severe reactions to the treatment.

Stephans team is now collaborating with several companies to fine-tune CAR-T treatments for cancer, according to Fred Hutch. And they believe their freeze-dried nanoparticles may prove useful in developing treatments for a range of other diseases, too, including HIV and blood disorders caused by defective hemoglobin.

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'Hit-and-run' gene therapy nanoparticles could enhance CAR-T ... - FierceBiotech

(KMSP) - Charlotte Gifford is almost 5 years old with dreams of looking like her favorite Disney princess.

Rapunzel, because she has the long hair, says Charlotte.

Charlotte lost her own long locks after being diagnosed last March with b-cell acute lymphoblastic leukemia, the most common form of leukemia to develop in children and young adults.

Once we got the word it was leukemia. Our world came down it crumbled, says Erica Gifford, Charlottes mom.

Erica and Adam Gifford are thrilled the Food and Drug Administration announced approval of the first gene therapy in the United States. Car t-cell gene therapy can be used for Charlottes type of leukemia, affecting anyone under 25 years old.

Its a new treatment with an entirely different flavor, says Dr. Daniel Weisdorf, Professor of Medicine and Chief Division of Hematology, Oncology and Transplantation. Its not a drug, but a way to take the patients own cells, their normal cells, and engineer the cells so they will specifically and uniquely attack the leukemia cells.

Weisdorf witnessed success from this treatment, as some patients from University of Minnesota Health and Masonic Cancer Center were part of the clinical trials.

The treatments are remarkably effective but complicated to administer because the patients get very sick, says Weisdorf.

The Leukemia and Lymphoma Society has helped fund research for decades, and today, Executive Director Teri Cannon is celebrating a major medical milestone.

Nowadays 90 percent of young people diagnosed with leukemia survive, says Cannon, Those kids that relapse and standard therapy doesn't work for them, 83 percent of the kids who have used car t-therapy in the clinical trial have survived. So that's going to bring us a lot closer to that 100 percent that is going to make parents happy.

As for Charlotte, she's doing well and in remission. Hopefully she'll never need the this newly approved gene therapy reserved for patients whose cancer has returned. For the Giffords, this major medical advancement offers their family and others optionsand hope.

You dont know how important it is until your own child is diagnosed with cancer, says Gifford.

Charlotte continues steroid, chemo and physical therapy. Her parents have started a Go Fund Me Page.

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FDA approves gene therapy that could fight type of leukemia - KMSP-TV

The US Food and Drug Administration (FDA) on Wednesday approved a "historic" treatment that genetically engineers a patient's own immune cells to fight childhood leukemia.

The procedure, known as CAR-T cell therapy, takes a patient's immune cells, or T-cells and white blood cells, and genetically modifies them to give a power boost to viciously target leukemia.

Once transfused back into the patient, the immune cells then attack leukemia cells for months or even years.

"We're entering a new frontier in medical innovation with the ability to reprogram a patient's own cells to attack a deadly cancer," said FDA Commissioner Scott Gottlieb. "New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses."

Read more:Fighting cancer with methadone - making chemotherapy more powerful

Last resort

The treatment was developed by Novartis Pharmaceuticals and the drug is known as Kymriah (tisagenlecleucel).

The immune system-altering treatment was approved for patients aged3 to 25 with a blood cancer called acute lymphoblastic leukemia (ALL),the most common form of childhood cancer in the US.

About 3,100 people under the age of 20 are diagnosed with ALL each year in the United States.Around20 percent of those with ALL fail to respond to traditional drug, bone marrow transplants and chemotherapy treatments. Typically, young patients with ALL who fail chemotherapy have only a 30 percent chance of survival.

The breakthrough treatment would only be used if the disease failed to respond to standard treatment.

The therapy would cost $475,000 (400,000 euros) per dose, but Novartis said anyone who didn't respond within a month would not have to pay. Typical treatments of ALL, such as bone marrow transplants, can run up to $800,000 in the first year.

Application to be filed in EU

According to studies, about 83 percent of patients responded to CAR-T cell therapy went into remission after three months.

The treatment does carry potential side effects, including an immune overreaction, fever, high blood pressure, neurological reactions, acute kidney injury and decreased oxygen.

Questions also remain about the drug's possible long-term side effects and ability to preventALL from coming back.

Due to their age, many of those suffering from the disease would be covered by their parent's health insurance or Medicare in the US.

The procedure is best known for treating a now 12-year-old girl named Emily Whitehead, who has been cancer-free for five years after being the first child to receive the experimental therapy.

An application for CAR-T is expected to be filed with the European Medicines Agency by the end of the year.

cw/cmk(AP, AFP)

Read the rest here:
US approves breakthrough gene therapy for childhood leukemia - Deutsche Welle

Hurricane Harvey Flooding Claims 6 Members Of Same Family

Members of the Saldivar family ranging from 6 to 84 perished inside a van swept by currents as they sought higher ground. (Patch)

U.S. OK's First Gene Therapy Treatment For Childhood Leukemia

The Food and Drug Administration on Wednesday signed off on the first gene therapy treatment in the U.S. that doctors say uses a patient's own cells to seek out and destroy deadly childhood leukemia. (Patch)

Legendary Basketball Coach Rollie Massimino Dead At 82

Legendary college basketball coach Rollie Massimino, who led the Villanova Wildcats to a storied NCAA Championship in 1985 against Georgetown University, has died, according to the chancellor of Keiser University, who expressed "heartfelt sadness" on behalf of the school. Massimino served as head coach of the Keiser men's basketball team for the past 12 years. He was 82. (Patch)

World's Worst Babysitters Leave 9-Month-Old At Long Island Casino

Three people, including two teens, were arrested after they left a 9-month-old baby at a Long Island casino Tuesday, police said. The trio was supposed to be babysitting the child, but a dispute with the baby's mother quickly sent things haywire. (Patch)

Indiana Couple Completes Decades-long Goal To Visit Every Cracker Barrel

An elderly couple from Goshen finished a decades-long mission over the weekend: to visit every Cracker Barrel location, WGN-TV reports. Ray and Wilma Yoder flew out to Tualatin, Oregon, so they could visit and eat at their 645th Cracker Barrel on Monday morning. (Patch)

Quick Hits

Trump Claims To Have Witnessed Harvey's 'Horror And Devastation' Firsthand - But Didn't (Patch)

Here's How To Throw A Killer Labor Day Party, According To Pinterest (Patch)

'Having A Baby Means Losing A Paycheck' For Pregnant Police Officer Forced On Unpaid Leave: ACLU (Patch)

Microsoft, Amazon Collaborate So Personal Assistants Can Chat (Patch)

Deer In The Headlights Detained On San Francisco-Oakland Bay Bridge (Patch)

Girl, 7, Halfway Through Hug-A-Cop Tour Across USA

Rosalyn Baldwin is on a mission. Her goal? To hug a law enforcement officer in every state of the USA. Spanning 21 states so far, the seven-year-olds journey has been shared via her website, which is maintained by her two sisters, OceanRose and Scholar24, as well as her Facebook page. (Patch)

Harvey Slams Southeast Texas: Helicopter Rescues; Heartbreaking Scene As Toddler Clings To Mother

People are being plucked from homes by helicopter, boats are going door to door and the governor is sending the National Guard to the area. And in Beaumont, one of the more heartbreaking scenes of the storm unfolded when rescuers saved a toddler who was clinging to the body of her mother, who had died. (Patch)

All Houston ISD Students To Receive 3 Free Meals Per Day This School Year

All Houston ISD students will eat for free during the 2017-18 school year thanks to a waiver of the required application process for the National School Lunch/Breakfast Program from the United States Department of Agriculture and the Texas Department of Agriculture. (Patch)

Hurricane Harvey Scam Alert: Beware Of ICE, HSI Impersonators

Houston Police Chief Art Acevedo said there are reports that people impersonating Homeland Security Investigations special agents. Acevedo said they are knocking on doors in the Houston area telling residents to evacuate in the aftermath of Hurricane Harvey presumably so these impostors can rob the empty homes, he said. (Patch)

Gas Prices Rising Thanks To Harvey, Says AAA

While Hurricane Harvey was bearing down on Texas and the Gulf Coast, drivers looking to fill up their tanks were greeted at the gas station with one of the largest one-week surges in gas prices this summer, according to AAA. Prices increased 4 cents to a nationwide average of $2.37 per gallon. (Patch)

Parade For Purple Heart Recipient Planned In Illinois

A United States Air Force veteran who was seriously wounded in Afghanistan a dozen years ago and given a small chance to live will be given a parade in the town where he attended high school. (Patch)

Hurricane Harvey: More Than 300 Gators East Of Houston Could Soon Escape Enclosure

As if things weren't bad enough in the Houston area amid Tropical Storm Harvey, up to 350 alligators at a sanctuary east of town could soon escape if water levels continue to rise, according to reports. (Patch)

Photo of Overjoyed Mom Becomes A Social Media Sensation

Her daughters, Hayley and Millaina, knew the photo of their mom jumping for joy with a glass of wine in her hand was being taken as a joke, but mom told Patch, "Those facial expressions are for real!!!" (Patch)

This Day In History

1422 King Henry V of England dies of dysentery while in France. His son, Henry VI becomes King of England at the age of 9 months.

1864 During the American Civil War, Union forces led by General William T. Sherman launch an assault on Atlanta.

1897 Thomas Edison patents the Kinetoscope, the first movie projector.

1962 Trinidad and Tobago becomes independent.

1993 Russia completes removing its troops from Lithuania.

Famous Birthdays

AD 12 Caligula, Roman emperor

1928 James Coburn, American actor

1944 Roger Dean, English illustrator and publisher

1946 Tom Coughlin, American football player and coach

1970 Debbie Gibson, American singer-songwriter, producer, and actress

Photo: Former Villanova head coach Rollie Massimino looks on prior to the 2016 NCAA Men's Final Four National Championship game between the Villanova Wildcats and the North Carolina Tar Heels at NRG Stadium on April 4, 2016, in Houston. Credit: Streeter Lecka/ Staff/ Getty Images Sport/ Getty Images

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Originally published August 31, 2017.

Read more from the original source:
Harvey Haunts Family Leukemia Gene Therapy Massimino Dies: Patch Morning Briefing - Patch.com