Monthly Archives: July 2017

We believe that when this treatment is approved it will save thousands of childrens lives around the world, Emilys father, Tom Whitehead, told the panel. I hope that someday all of you on the advisory committee can tell your families for generations that you were part of the process that ended the use of toxic treatments like chemotherapy and radiation as standard treatment, and turned blood cancers into a treatable disease that even after relapse most people survive.

The main evidence that Novartis presented to the F.D.A. came from a study of 63 patients who received the treatment from April 2015 to August 2016. Fifty-two of them, or 82.5 percent, went into remission a high rate for such a severe disease. Eleven others died.

Its a new world, an exciting therapy, said Dr. Gwen Nichols, the chief medical officer of the Leukemia and Lymphoma Society, which paid for some of the research that led to the treatment.

The next step, she said, will be to determine what we can combine it with and is there a way to use it in the future to treat patients with less disease, so that the immune system is in better shape and really able to fight. She added, This is the beginning of something big.

At the meeting, the panel of experts did not question the lifesaving potential of the treatment in hopeless cases. But they raised concerns about potentially life-threatening side effects short-term worries about acute reactions like those Emily experienced, and longer-term worries about whether the infused cells could, years later, cause secondary cancers or other problems.

Oncologists have learned how to treat the acute reactions, and so far, no long-term problems have been detected, but not enough time has passed to rule them out.

Patients who receive the treatment will be entered in a registry and tracked for 15 years.

Treatments involving live cells, known as biologics are generally far more difficult to manufacture than standard drugs, and the panelists also expressed concerns about whether Novartis would be able to produce consistent treatments and maintain quality control as it scaled up its operation.

Another parent at the meeting, Don McMahon, described his son Connors grueling 12 years with severe and relapsing leukemia, which started when he was 3. Mr. McMahon displayed painful photographs of Connor, bald and intubated during treatment. And he added that chemotherapy had left his son infertile.

A year ago, the family was preparing for a bone marrow transplant when they learned about the cell treatment, which Connor then underwent at Duke University. He has since returned to playing hockey. Compared with standard treatment, which required dozens of spinal taps and painful bone marrow tests, the T-cell treatment was far easier to tolerate, Mr. McMahon said, and he urged the panel to vote for approval.

A third parent, Amy Kappen, also recommended approval, even though her daughter, Sophia, 5, had died despite receiving the cell treatment. But it did relieve her symptoms and give her a few extra months. Sophias disease was far advanced, and Ms. Kappen thought that if the treatment could have been given sooner, Sophia might have survived.

We hope that more families have a longer time with their children fighting this evil disease, and our children deserve this chance, she said.

The treatment was developed by researchers at the University of Pennsylvania and licensed to Novartis.

Use will not be widespread at first because the disease is not common. It affects only 5,000 people a year, about 60 percent of them children and young adults. Most children are cured with standard treatments, but in 15 percent of cases like Emilys and Connors the disease does not respond, or it relapses.

Analysts predict that these individualized treatments could cost more than $300,000, but a spokeswoman for Novartis, Julie Masow, declined to specify a price.

Although the figure may seem high, people with cancer often endure years of expensive treatment and repeat hospital stays that can ultimately cost even more.

Because the treatment is complex and patients need expert care to manage the side effects, Novartis will initially limit its use to 30 or 35 medical centers where employees will be trained and approved to administer it, the company said.

As to whether the treatment, known as CTL019 or tisagenlecleucel (pronounced tis-a-gen-LEK-loo-sell), will be available in other countries, Ms. Masow said by email: Should CTL019 receive approval in the U.S., it will be the decision of the centers whether to receive international patients. We are working on bringing CTL019 to other countries around the world. She added that the company would file for approvals in the European Union later this year.

By late November 2016, 11 of the 52 patients in the study who went into remission relapsed. Twenty-nine were still in remission. Eleven others had further treatments, like bone marrow transplants. One patient was not available for assessment. Three who had relapses died, and one who did not relapse died from a new treatment given during remission. The median duration of remission is not known because it has not been reached: Some patients were still well when last checked.

Researchers are still debating about which patients can safely forgo further treatment, and which might need a bone marrow treatment to give the best chance of a cure.

The treatment requires removing millions of a patients T-cells a type of white blood cell often called soldiers of the immune system and genetically engineering them to kill cancer cells. The technique employs a disabled form of H.I.V., the virus that causes AIDS, to carry new genetic material into the T-cells to reprogram them. The process turbocharges the T-cells to attack B-cells, a normal part of the immune system that turn malignant in leukemia. The T-cells home in on a protein called CD-19 that is found on the surface of most B-cells.

The altered T-cells are then dripped back into the patients veins, where they multiply and start fighting the cancer.

Dr. Carl H. June, a leader of the University of Pennsylvania team that developed the treatment, calls the turbocharged cells serial killers. A single one can destroy up to 100,000 cancer cells.

Because the treatment destroys not only leukemic B-cells but also healthy ones, which help fight germs, patients need treatment to protect them from infection. So every few months they receive infusions of immune globulins.

In studies, the process of re-engineering T-cells for treatment sometimes took four months, and some patients were so sick that they died before their cells came back. At the meeting, Novartis said the turnaround time was now down to 22 days. The company also described bar-coding and other procedures used to keep from mixing up samples once the treatment is conducted on a bigger scale.

Michael Werner, a lawyer and expert on gene and cell technologies and regulation, and a partner at Holland and Knight in Washington, said that results so far proved that T-cell treatment works.

The fact that it can be done means more people will go into the field and more companies will start developing these products. He added, I think were in for really exciting times.

A version of this article appears in print on July 13, 2017, on Page A1 of the New York edition with the headline: F.D.A. Panel Urges New Living Drug To Fight Cancer.

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FDA Panel Recommends Approval for Gene-Altering Leukemia Treatment - New York Times

Dr. Erin Kinney used to assess patients nutritional needs with an analysis of their eating habits and family and medical histories. Nowadays the Arnold naturopathic doctor is delving deeper and also analyzing her patients' genetic makeup.

She is part of a growing number of dieticians, nutritionists and holistic doctors practicing nutritional genetics, or looking at how variations in genes can modify the affects of nutrients on health. The health care providers are using the information to help patients figure out which foods they should eat or avoid, and that best suits their biological makeup.

"We are now learning that maybe you have a certain genetic disposition to not making enough of a certain enzyme," said Kinney, who is also president of the Maryland Naturopathic Doctors Association. "It is really changing the way we are going to be able to tailor our treatments for patients."

Dieticians for years have used genetics on a limited basis, looking at mutations in one particular gene that may make patients prone to disease or more likely to have certain health conditions. For example, patients who are lactose intolerant can't break down the lactose found in dairy products because of a mutation in the lactose gene. So they suffer with gas and other uncomfortable digestive problems after drinking milk or eating cheese or ice cream.

The sequencing of the human genome - or the mapping of every gene in the body - has enabled not just dieticians, but all doctors, to use genetics in a more comprehensive way. A doctor can look at a patient's entire genetic makeup to determine, for instance, if they have multiple gene mutations that would make them more prone to obesity or cardiovascular disease.

Algerina Perna / Baltimore Sun

Most human genes are the same from person to person, but some have variations. The most common type of variation is known as a SNP (pronounced "snips"), or single nucleotide polymorphisms, and accounts for difference in physical characteristics of people, including eye and hair color or blood type. Different SNPs can also determine if someone will be more prone to developing certain diseases.

"The genome is the gold mine where genes can be targeted and we can learn more about how nutrients can play a role in people's health," said Braxton Mitchell, a genetic epidemiologist at the University of Maryland School of Medicine who studies the genetics of complex diseases.

But Mitchell and others caution the field is still emerging and that ongoing research is needed to sort out the many ways genetics could be used to guide nutrition and food choices.

The Academy of Nutrition and Dietetics wrote a position paper in 2014, published in the organization's journal, that said nutritional genomics is not ready for widespread use.

"The practical application of nutritional genomics for complex chronic disease is an emerging science and the use of nutrigenetic testing to provide dietary advice is not ready for routine dietetics practice," the position paper said. "Registered dietitian nutritionists need basic competency in genetics as a foundation for understanding nutritional genomics; proficiency requires advanced knowledge and skills."

A spokesman for the organization said it still stands behind that statement.

"It is pretty complicated right now because genes are complicated," said Ginger Hultin, a dietician and spokeswoman for the Academy of Nutrition and Dietetics. "It is not generally enough to just look at a single gene variation. There is so much to look at on genes and you also have to consider a person's lifestyle and how they interact with the environment."

The Maryland University of Integrative Health held its first ever symposium last month to encourage what they called "knowledge sharing" on the interaction between genetics and dietary factors. The conference, held in partnership with the Maryland Naturopathic Doctors Association, was focused on giving health care providers practical advice on how to incorporate nutritional genomics testing, counseling and treatment into clinical practice.

Christy Williamson, an adjunct professor at the university who also owns a genetic nutritional company, said that variations in genes might mean that two people with diabetes might need different diets customized for their biological makeup. Other people might have a gene variation that causes them to need more exercise to get enough molecular oxygen to lose weight.

There is also the possibility that a mutation might not have any affect on the body.

"Certain things are epigenetically activated," Williamson said. "That doesn't mean everybody who has a gene variation will get that particular disease. Genetics kind of loads the gun and the environment pulls the trigger."

Lifestyle can also offset the affects of the gene variation. If your gene makes you more prone to gain weight, for instance, extra exercise could help you fend off weight gain.

"You can have bad genes, but if you have a good lifestyle you can change the way your genes are expressed," Kinney said. "Your body can get back into balance despite that your body has these gene mutations."

Companies like 23andMe, Vitagene and Nutrigenomix will map a patient's genome using a swab of saliva. Kinney then uses a system called Opus 23 Pro that analyzes the data.

Kristen Kissik, an Annapolis dance and yoga instructor, was one of those patients who had her genome analyzed. Kissik wanted to make sure she was doing everything she could to ensure she had the most optimal health. She had been eating foods she knew would help reduce inflammation, improve her thyroid functions and ease her gluten sensitivity.

"The stuff I got almost affirmed my intuition," Kissik said of the results her genome analysis. "I know I had an issue and it is in my genes."

Mitchell, the University of Maryland epidemiologist, believes nutritional genomics has the potential to one day help decide which diets are best for people. He predicts it could also eventually lead to new treatments for various diseases and medical conditions. But more research needs to be done to validate the potential benefits.

"There is a lot going on in the field," he said. "We have to be skeptical when see results from early studies. We want to see results repeated before we believe them."

amcdaniels@baltsun.com

Twitter.com/ankwalker

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Genetics playing a growing role in intersection of nutrition and health - Baltimore Sun

July 13, 2017 by Nora Dunne Localization of pro-fibrotic hormones in heart muscle cells (green), which synthesize and release transforming growth factor-beta (red) following cardiac injury. Nuclei are shown in blue. Credit: Northwestern University

Northwestern Medicine scientists have identified a novel molecular mechanism that regulates scar formation in the heart, a common manifestation of aging and nearly every form of heart disease. The discovery was published in the journal Circulation.

The scientists showed that heart muscle cells called cardiomyocytes are a principal source of the molecular signals that drive scarring in the heart, a process known as cardiac fibrosis.

"Historically, these signals were thought to arise from other cell types in the heart," explained Panagiotis (Peter) Flevaris, MD, PhD, '12, '17 GME, instructor of Medicine in the Division of Cardiology and first author of the paper. "We also identified the gene that serves as the master regulator of the synthesis and release of pro-fibrotic signals from heart muscle cells across different species."

First, Flevaris and colleagues showed that a familial mutation in that gene, which encodes the protein plasminogen activator inhibitor-1 (PAI-1), leads to spontaneous cardiac fibrosis in otherwise healthy individuals in an Old Order Amish community. The findings in the human population confirmed previous observations in mice lacking the gene for PAI-1.

Importantly, the scientists found that a protein called bone morphogenetic protein 7 (BMP7) can prevent the generation of fibrotic signals by cardiomyocytes and may be able to serve as a future therapy for cardiac fibrosis.

"Tissue fibrosis is the leading cause of organ failure, but persists as one of the most pressing global health problems due to lack of effective pharmacotherapies. Currently, the only cure for cardiac fibrosis is heart transplantation," said Flevaris, who completed this research during a post-doctoral fellowship in the Department of Medicine's Physician-Scientist Training Program, working with senior author Douglas Vaughan, MD, Irving S. Cutter Professor of Medicine and chair of Medicine.

"Supported by clinical and functional data, our work provides exciting new evidence that modulation of cardiomyocyte signals by BMP7 represents a unique therapeutic strategy to prevent cardiac fibrosis," Flevaris added. "This discovery not only provides a novel paradigm for how the heart muscle generates signals following injury, but also has the potential to transform healthcare for the heart failure population at large."

Explore further: Study shows cardiac fibrosis reversal through gene targeting in heart failure models

More information: Panagiotis Flevaris et al. PAI-1 Controls Cardiomyocyte TGF- and Cardiac Fibrosis, Circulation (2017). DOI: 10.1161/CIRCULATIONAHA.117.028145

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Root of cardiac fibrosis defined - Medical Xpress