Heart Failure

25
May 2016
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Dr. Duncan Stewart: "Be wary of any stem cell therapy that is fee-based and has not been validated through a complete clinical trial process."

Researcher/clinician Stewart to lead OIRM’s ‘next phase of growth’

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The Ontario Institute for Regenerative Medicine (OIRM) today named Dr. Duncan Stewart, one of Canada’s leading stem cell researchers, as its new President and Scientific Director.…

The Ontario Institute for Regenerative Medicine (OIRM) today named Dr. Duncan Stewart, one of Canada’s leading stem cell researchers, as its new President and Scientific Director.

“It will be my pleasure to serve OIRM by helping the organization, its researchers, trainees and staff to fulfill their passion to make a difference for all Ontarians,” Dr. Stewart said in a media release.

He succeeds Dr. Janet Rossant, who launched OIRM in 2014 but recently took on a new role as the Gairdner Foundation’s President and Scientific Director.  She praised Dr. Stewart “the perfect choice to lead OIRM as it moves into the next phase of growth.”

The head of research at The Ottawa Hospital and a professor at the University of Ottawa, Dr. Stewart co-leads an early stage clinical trial to test the use of stem cells to treat septic shock. It has shown promising preliminary results.  And he is conducting a Phase 2 trial to investigate the use of genetically enhanced stem cells to treat heart attack patients.

Dr. Stewart will remain in Ottawa to pursue his lab and clinical research activities and to carry on as Executive Vice-President of Research at The Ottawa Hospital.

“Given the breadth of his skills, Duncan brings unique perspectives on the regenerative medicine environment, particularly in the critical area of clinical trials and the development of new treatments, which is a key part of our mission,” said Sharon Colle, Chair of the OIRM Board and President and CEO, of The Foundation Fighting Blindness.

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27
Nov 2014
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Two sure signs of the increasing importance of investing in stem cells

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Heart surgery survivor Charlotte Desbiens with her parents

“I don’t want any other person’s parents going through what my parents went through,” says Charlotte Desbiens, a remarkable little girl who underwent three heart surgeries before age three.…

Heart surgery survivor Charlotte Desbiens with her parents

Heart surgery survivor Charlotte Desbiens with her parents

“I don’t want any other person’s parents going through what my parents went through,” says Charlotte Desbiens, a remarkable little girl who underwent three heart surgeries before age three.

Charlotte, with a sense of compassion well beyond her years, tells her story in a powerful video announcing a $130-million gift to create the Ted Rogers Centre for Heart Disease.  The unprecedented donation will allow researchers to explore “the mechanism of what goes wrong in heart function,” says Dr. Janet Rossant, Chief of Research at the Hospital for Sick Children. Hers is one of the three Toronto-based organizations partnering to create the Centre.

Stem cell research and development is a major component of the work the Centre will undertake. While SickKids will focus on harnessing the genomics to decode the genetic foundations of cardiac disease and the University Health Network (UHN) will target the translation of research discoveries into the delivery of care for patients, the University of Toronto (U of T) will combine stem cell technology with new approaches in cellular and tissue engineering to find ways to regenerate heart muscle, coronary vessels, and heart valves.

The Centre is named after Edward Samuel “Ted” Rogers, Jr., the telecommunications pioneer and President and CEO of Rogers Communications Inc. until his death in 2008. According to the UHN press release, the Rogers family’s donation is the largest monetary gift ever made to a Canadian health care initiative. It will be matched with $139 million funds from SickKids, UHN, and U of T for a total investment of $269 million.

The Nov. 20th Rogers Centre announcement was one of two significant endorsements of stem cell R&D in recent days. On Tuesday, the Government of Ontario awarded $3.1 million to the Ontario Stem Cell Initiative (OSCI) and the Centre for Commercialization of Regenerative Medicine (CCRM) to establish the Ontario Institute for Regenerative Medicine (OIRM).

OIRM will focus on translating stem cell research into new cures and treatments for degenerative diseases.  Specific “disease challenge” teams have been identified:  Dr. Valerie Wallace at the U of T leads a team tackling age-related macular degeneration, the leading cause of blindness in the developed world; Dr. Gordon Keller, also at the U of T, is focusing efforts on treatments for ventricular fibrillation, the leading cause of cardiac arrest; and Dr. Mick Bhatia at McMaster University will advance the use stem cells to get the immune system to destroy tumours.  The announcement was covered in the Globe and Mail.

The key takeaway from both these announcements is that it will take a concerted effort from many different players to tackle diseases that have baffled medical science for too long. And it will take time. As noted in the Globe piece, OIRM’s $3.1 million only covers the awarded projects for a single year. “In comparison, California has invested $3 billion in regenerative medicine in the past decade and has several promising treatments now in clinical trials.”

As the newspaper reports, the Canadian Stem Cell Foundation, representing a coalition of scientists, medical professionals, health charities, industry experts and philanthropists, “called on the federal government in October to commit half a billion dollars over a decade to boost stem cell research and development in Canada.”

The Canadian Stem Cell Strategy & Action Plan is a 10-year plan to accelerate the safe translation of research discoveries into new cell-based therapies, products and technologies. Just as the Rogers Centre for Heart Disease has set specific goals — to reduce hospitalization for heart failure by 50% in the next 10 years — the Canadian Stem Cell Strategy keeps an eye on the prize: it’s an aggressive Action Plan for Canada to lead the way in bringing up to 10 breakthrough therapies to the clinic by 2025. It will mean Canadians will have access to effective new treatments and will reduce the burden of disease on caregivers. It will also create jobs, enhance productivity and strengthen our economy.

Find out more about the Strategy here.

Because, ultimately, it is all about finding ways to cure diseases so that wonderful little girls like Charlotte live long and happy lives. And so that parents don’t have to worry.

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09
Apr 2014
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Mini-heart Screen Capture

Thinking outside the heart

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Stem cell derived mini-heart can pump blood through sluggish veins

A U.S.-based researcher has come up with what she believes is a stem cell solution for sluggish blood flow that could knock the socks off the current standard of care.…

Stem cell derived mini-heart can pump blood through sluggish veins

A U.S.-based researcher has come up with what she believes is a stem cell solution for sluggish blood flow that could knock the socks off the current standard of care.

“Compression stockings have been used since antiquity,” says Dr. Narine Sarvazyan, a researcher at George Washington University in Washington, DC. “So we really haven’t made much progress in treating chronic venous insufficiency.”

The condition is common, affecting between 20-30% of people over the age of 50. It can be particularly distressing for people with diabetes, causing non-healing ulcers to form on their legs or ankles. It can also affect people who are paralyzed and those recovering from surgery.

Dr. Sarvazyan’s solution is to implant a “mini-heart” made of stem cell derived heart muscle cells called cardiomyocytes at the site where the blood is stagnating.  The cells form a cuff that wraps around the problem vein while rhythmically contracting and releasing to move the blood along. You can see a short video of how it works here.

The invention of the mini-heart has caused quite a stir online.  It has been picked up by the Huffington Post, Science Daily and Business Standard

So far, Dr. Sarvazyan has only created “in vitro” (Petri dish) versions of the mini-hearts in her lab. Her next step, after finalizing the design, will be to move to animal tests with rats and, ultimately, pigs. In a best-case scenario, she hopes to begin clinical trials with people after about two years.

The advantage is the mini-hearts can be tailor-made from stem cells extracted from the patient’s own fatty tissue so that there will be no danger of rejection and little risk of inflammation.

“It’s a very different application,” says Dr. Sarvazyan. “Most people who work with these cardiomyocytes have a goal of repairing cardiac muscles. That is pretty much where everyone is aiming.  But the idea came into my mind that we can use the same tissue and actually use it in different locations much more easily. You don’t have to have that much structured muscle. It doesn’t have to have much force. It’s easier to vascularize because it’s smaller.”

Dr. Sarvazyan outlines the advantages in a paper called Thinking Outside the Heart, published, in the Journal of Cardiovascular Pharmacology and Therapeutics.

“So far I don’t see any downsides,” she told Stem Cell NewsDesk.  “Of course, nature is much smarter than us. It’s possible when we put it in animals, something may happen that we could not predict.  I can’t say for sure that it will work — we definitely need to test it.”

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25
Mar 2014
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Tiny hearts = big deal for drug testing

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When the subject of using stem cells to treat disease comes up, most of us have an image of doctors injecting or infusing these building-block cells into a patient to stimulate the repair of their traumatized tissue or dysfunctional organs.…

When the subject of using stem cells to treat disease comes up, most of us have an image of doctors injecting or infusing these building-block cells into a patient to stimulate the repair of their traumatized tissue or dysfunctional organs.

We’ve written about this approach several times in this space — most recently reporting on a clinical trial to test stem cells in spinal cord injury.  We also reported on a 100-participant study led by Dr. Duncan Stewart at the Ottawa Health Research Institute infusing genetically enhanced blood stem cells into damaged hearts to generate healthy tissue, minimize scarring and prevent heart failure.

Those kinds of studies are called in vivo, meaning “within the living.” But researchers are also opening up entirely different front in the war on disease: using stem cells to create “models” of diseased tissue or organs for testing drugs. Called in vitro (literally, “within the glass” to signify experiments carried out in a Petri dish or test tube), these studies essentially set up a disease straw man for a potential therapy to knock down.

There are advantages to this approach: it skips the pre-clinical animal testing stage that can be a labour-intensive, time-consuming exercise. Imagine the frustration of spending months testing a new drug on rats only to find it’s a no-go. Also, what can show great promise in testing with genetically engineered, immuno-suppressed rats often doesn’t translate into something that will work on real, live, normal human beings.

One of the more promising examples of this kind of work is underway at the University of Toronto’s Institute of Biomaterials & Biomedical Engineering and the McEwen Centre for Regenerative Medicine. Researchers there have developed the first-ever method for creating living, three-dimensional human heart tissue that behaves just like the one pumping blood through your body as you read this. Their findings were published in the Proceedings of the National Academy of Science recently and, so far, have been picked up by 10 media outlets.

“It means basically having hundreds of small versions or models of hearts in one dish, which we can test drugs on to determine which one actually has positive effects,” explains Nimalan Thavandiran, a PhD student in the labs of Drs. Peter Zandstra and Milica Radisic, and lead author of the study.

The ultimate goal, he says, is to create a heart micro tissue that is healthy and then “artificially apply an insult to it” to make it more like a diseased heart. These damaged micro hearts can then be treated with drugs — some that are already on the market for treating other conditions — to see which ones are helpful.

The micro heart tissue can also do service to test the cardio-toxicity of drugs used to treat other conditions. “Often times, a drug to treat cancer will make it to the later phases of a clinical trial and then fail because of side effects on either liver or the heart. So this is why it is important to have human cell-based models, like cardiac or liver models to see early on if these drugs have any adverse effects. And if they do, you can do two things: you can either scrap the drug or you can actually figure out how to molecularly modify it to prevent the toxic effect.”

In the extremely expensive world of drug testing, where it can take hundreds of millions of dollars and many years to test a new drug, having a stem cell-derived micro tissue model represents a huge saving in time, money and resources that could be better spent elsewhere. That’s why many labs across the globe are working to create these models.

With the publication of their paper, Nimalan Thavandiran and his colleagues have shown how to significantly improve the formula for creating stem cell-derived cardiac tissue that behaves like more mature heart tissue. They have come closer than anyone to getting the mix right, factoring in the electrical and mechanical stimulation a heart experiences.

“The heart is consistently both being filled with blood and pumping blood, and so there is a constant mechanical force,” he says. “At the same time, the heart is constantly receiving electrical signals which help maintain synchronicity. All this is very difficult to recreate in a dish.”

They still have further to go, he says. “The ultimate goal is to be able to recreate a perfect micro environment for the heart so that we have an ideal model to screen drugs with.” But they are closing in on what could soon emerge as an important step in drug-testing.

“Until recently, researchers didn’t have the right micro fabrication techniques, the right materials, differentiation protocols, the right understanding of what co-factors are involved with these stem cell-derived heart cells. Now we have a relatively good understanding of all of these things.  It’s just the matter of putting it all together.”

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26
Sep 2013
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StewartGarrows400EN

Will enhanced stem cells mend broken hearts?

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The unveiling of a clinical trial to test the use of genetically enhanced stem cells to rebuild badly damaged hearts captured major media attention in early September.…

The unveiling of a clinical trial to test the use of genetically enhanced stem cells to rebuild badly damaged hearts captured major media attention in early September.

CBC News, the Sun and Postmedia newspapers all called the trial “groundbreaking” and gave it prominent play. CTV  called it a “world-first clinical trial.” The Globe and Mail  coverage was somewhat more restrained but went into fine detail to explain how the patient’s own blood stem cells are enhanced with a gene called endothelial nitric oxide synthase (eNOS) that is then infused into the heart at the site of the damage.

It didn’t hurt that the Ottawa Hospital Research Institute, where Principal Investigator Dr. Duncan Stewart is CEO and Scientific Director, was able to put a gentle human face on complicated science by presenting Patient No. 1. Sixty-eight-year-old Harriet Garrow of Cornwall, Ontario suffered a major, heart-stopping myocardial infarction in July.  Holding hands with her husband Peter Garrow, she was amiable, articulate and authentic.  Reporting the news Sept. 10, the Aboriginal Peoples Television Network  highlighted her heritage, headlining its story “Mohawk woman in centre of ground breaking medical treatment.”

This is a double-blind study – meaning neither the investigators nor the 100 participants in Ottawa, Montreal and Toronto will know who received the souped-up stem cells or the comparative controls of ordinary stem cells or placebos until after the results are in. That doesn’t matter to Mrs. Garrow, who, at the very least, is getting the best of current cardiac care. “I am thrilled to play a part in this research that could help people like me in the future and, who knows, perhaps even my children and grandchildren,” she said in the OHRI’s media release.

A decade of work

Investigators will start analyzing the results after Patient No. 100 has been enrolled and treated – more than two years from now. By that time, Dr. Stewart will have put 10 years into the project he originally started at St. Michael’s Hospital in Toronto.

But things could happen quickly after that.

“Most major medical centres in Canada and the United States have the capacity to do this kind of cell manufacturing, “ says Dr. Stewart. “So, if we allow ourselves to dream a bit, that this really is a very positive trial with major improvements, I think it could be adopted quite quickly.”

The implications – in terms of thousands of lives that could be saved and millions of dollars in health care costs avoided – are immense. About 70,000 Canadians have heart attacks every year. Dr. Stewart estimates that about one-third of those, around 23,000, suffer damage severe enough to require this level of intervention.

“This segment of the infarct population is one that’s going to cost an awful lot of money because before they die they are going to develop heart failure. They’re going to be having multiple prolonged hospital admissions and require implantation of defibrillators and are going to have all kinds of other treatments that cost the system a lot of money.”

Other trials using ordinary stem cells have shown some positive effect on repairing heart tissue, but nothing that would spark widespread change in how heart attack patients are treated. The difference here is these stem cells have rejuvenated with eNOS to do a more effective repair job.

“It’s always been our view that getting the most robust therapy requires some manipulation of the cells, particularly when you’re using the patient’s own cells,” says Dr. Stewart. “The cells are the same age as the patient, which is usually 60 or 70 years old, and they have been exposed to the same factors that produced heart disease in the first place. We know they don’t work well. But if we can recover the activity of these cells we’re going to get more benefit.”

It all depends, of course, on The Big If: If it works.

Given the rigorous controls and criteria included in the clinical trial,  the answer should be obvious within three years.

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