The Ottawa Hospital

28
Feb 2017
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UK study further substantiates stem cell treatment for MS

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Last summer we blogged about a team at The Ottawa Hospital that had proved a stem cell/chemo combo treatment could halt the progression of multiple sclerosis (MS) and — in some cases — help patients recover from the autoimmune disease.…

Last summer we blogged about a team at The Ottawa Hospital that had proved a stem cell/chemo combo treatment could halt the progression of multiple sclerosis (MS) and — in some cases — help patients recover from the autoimmune disease.

Now comes news from the United Kingdom that further substantiates the work of Drs. Harry Atkins and Mark Freedman in showing that using bone marrow stem cell transplants to rebuild an MS patient’s immune system can prevent the disease from worsening and dramatically improve mobility and freedom from pain for some.

The Atkins-Freedman study, published in the prestigious Lancet journal, focused on two dozen patients treated over a decade. The UK study, published last week in JAMA Neurology, reviewed 281 patients tracked over five years. Led by Dr. Paolo Muraro of Imperial College London, the study found the treatment prevented symptoms of severe disease from worsening for five years for almost half of the patients treated.  Drs. Atkins and Freedman co-authored the UK study and  results from their work were included in the review.

Among patients with relapsing MS, nearly three in four saw no worsening of their symptoms five years after treatment, while younger patients with less severe forms of the disease were more likely respond to the therapy. Most of the patients, though, had progressive MS, which is more severe.  Among them, one in three experienced no worsening of symptoms, according to a report by Imperial College.

MS occurs when a person’s immune system misfires and begins attacking nerves in the brain and spinal cord. Currently, there is no treatment for sever, progressive MS.

In essence, the new approach, which is called autologous hematopoietic stem cell transplantation, involves extracting the patient’s own bone marrow stem cells and fortifying them, then destroying their immune system through chemotherapy. The stem cells are then transplanted back into the patient to rebuild the immune system — ideally without the disease.

The stem cell/chemo treatment is not for everyone who has MS — young people with more robust stem cells tend to respond better than older patients — and it comes with risks. Eight patients died following the treatment.

Dr. Muraro said the risks must be weighed against the benefits: “We previously knew this treatment reboots or resets the immune system – and that it carried risks – but we didn’t know how long the benefits lasted. In this study, which is the largest long-term follow-up study of this procedure, we’ve shown we can ‘freeze’ a patient’s disease – and stop it from becoming worse, for up to five years.”

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03
Jan 2017
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CTV tells story of Dan Muscat’s ‘180-degree’ turnaround

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In this blog and in our Fall/Winter newsletter we told the story of Dan Muscat, the St. Thomas, Ontario jeweler who has seen remarkable reductions in the symptoms of his scleroderma — a painful and deadly disease that turns the skin of its victims into cement-like hardness and then petrifies their internal organs.…

In this blog and in our Fall/Winter newsletter we told the story of Dan Muscat, the St. Thomas, Ontario jeweler who has seen remarkable reductions in the symptoms of his scleroderma — a painful and deadly disease that turns the skin of its victims into cement-like hardness and then petrifies their internal organs.

Over the summer, Dan underwent an experimental stem cell therapy at The Ottawa Hospital under the care of Dr. Harry Atkins, who has done outstanding work in treating patients with other autoimmune diseases such as multiple sclerosis, Stiff Person’s Syndrome and Crohn’s disease using a combination chemotherapy/stem cell approach.

Avis Favaro reported on Dan’s “180-degree” turnaround on CTV National News last night, telling Dan’s powerful story. You can watch it here.

After the initial report, the CTV website provides a four-minute interview with Dan that goes into greater detail, along with interviews with Dr. Atkins and James Price, President and CEO of the Canadian Stem Cell Foundation, who says “Dan’s story is an exciting one for the field.”

As Ms Favaro says at the end of her report, Dan continues to get improve and is now able to walk three kilometres on a treadmill. While the extreme treatment isn’t for all scleroderma patients — it comes with potentially fatal risks — it offers new hope where none existed before.

In the wake of the CTV story on Dan,  The Ottawa Hospital has produced an online resource for people seeking more information about chemo/stem cell treatments for scleroderma and other autoimmune diseases like MS and Stiff Person’s Syndrome. You can find it here.

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20
Jul 2016
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Dr. Duncan Stewart

Q&A with Duncan Stewart, new head of the Ontario Institute for Regenerative Medicine

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Dr.  Duncan Stewart is one of the busiest people in regenerative medicine in Canada.  An internationally respected cardiac specialist, he leads a three-city clinical trial investigating the potential benefits of genetically enhanced stem cells in healing severe heart attacks. …

Dr.  Duncan Stewart is one of the busiest people in regenerative medicine in Canada.  An internationally respected cardiac specialist, he leads a three-city clinical trial investigating the potential benefits of genetically enhanced stem cells in healing severe heart attacks.  He also heads research at The Ottawa Hospital and teaches at the University of Ottawa.  Dr.  Stewart was recently named President and Scientific Director of the Ontario Institute for Regenerative Medicine (OIRM).

Q: Along with your research, clinical work and teaching, you’ve now taken on the role of Scientific Director for OIRM.  How do you juggle it all?

A: It’s a matter of prioritization.  My day job is here at the Ottawa Hospital Research Institute (OHRI) and that’s a fairly significant operation because we’re one of the largest in Canada now.  I have a wonderful team here; it’s well set up and it can be done reasonably.

My clinical practice is really a hobby right now.  I see patients in a clinic that specializes in what I’m interested in: pulmonary hypertension and serious cardiac heart problems.  It’s personally rewarding; it keeps me sane and I can do something where I think I’ve made a difference.  But it’s about a half-a-day a week.  I don’t do much teaching … two or three or four courses a year.

I love doing research.  I thought that when I took on these other responsibilities maybe I’d have to reduce that, but I’ve been successful at getting funding and the projects have been successful, so it’s larger.  It’s aligned with the other things I do.  The priorities of the OHRI are well aligned with the kind of research I do and the new opportunity with the OIRM, again, is very aligned.

Q: What are you excited about in the field of stem cells and regenerative medicine?

A: I’m excited about moving it more into the clinic.  But we have to be realistic about the expectations.  When we’re doing these clinical trials, we are doing them to learn.  There are all kinds of issues we have to get right in order to unlock the real potential of these therapies.  It’s going to take a fair bit of work and a number of clinical trials and going back to the bench to refine approaches before we get to the point where we can do the dramatic things we hope to do.

If you look at the pace of development for other disruptive technologies, in the early stages they didn’t look that fantastic.  It’s similar to the early days of the personal computer.  It was very frustrating.  You did it for fun, really, for word processing, but it was hardly earth-shaking.  Now you look at a PC and it can do what NASA used to do with a great big mainframe.  A smartphone can do absolutely everything.  The technology has evolved to the point where it’s changed the whole landscape.

I think that’s true also in the cell and gene therapy space.  When I look at what’s going on in our lab and what’s going on globally, there is so much opportunity to advance this and improve the sophistication.  The potential is just huge.  What we’re doing in clinical trials, because we’re doing things that are well-tested and safe, tends to be using technologies that were developed 10 years ago.  So it’s well behind the cutting edge of where the field is going.  It takes that much time to get to clinical trials.  I think what we’re looking for is more proof of principle, where we can — in a modest way — achieve some of our goals and learn where the opportunities are to make things better.

Q: So the key is to move into clinical trials?

A: It’s important even when you’re at the early stages of development of technologies, in a safe and responsible way, to get the experience in the context of the patient population that has the disease.  Because you can never model all this completely in the lab.  You may have a great technology, but unless you can use it in the real world patient population you could have a problem.

A good example is autologous cell therapy (therapies in which the patient’s own stem cells are used).  For the chronic diseases we want to treat with regenerative approaches, we’re usually dealing with older patients who have risk factors and various diseases.  All that reduces their regenerative activity of their own cells: their stem cells aren’t very good.  So, you can do all the testing you want in young, healthy models but you’ve got to get at that problem.  We need to find why these cells don’t work and what we can do to recover activity.  Induced pluripotent stem cell technology (drawing cells from skin and reprogramming them back to an embryonic stem cell-like state) not only produces a pluripotent stem cell, it turns the age back to zero.  There are other issues with that in terms of safety and whether it’s ready for prime time, but there are already clinical trials starting with that technology.  That’s one way.  There are other ways, maybe more subtle ways, to recover regenerative activity.  These are the issues that come to the fore when you start to translate therapies into clinical trials.

Q: There is some frustration that things haven’t moved faster.  Stem cells have been touted as being able to cure a number of diseases and that it’s going to happen soon.  What’s holding the field back?

A: The frustration is probably our own doing: we bought into the hype or generated the hype too much.  We need to set the expectations at a realistic level.  It does no good to say we’re going to cure a disease with an approach when we’re not really there yet.  It’s important that we do the clinical trials.  It’s important to understand what benefit we get, if any, with a simple, early therapy so we can start improving it.  But we need to understand that this is going to be a somewhat incremental process at the beginning.  It’s not going to be earth-shattering and necessarily curative in the first iteration.  Setting that expectation will decrease that frustration.

The reality is, this takes time.  It’s a very different activity to be moving these approaches into clinical trials than doing the fundamental research.  People who have made major discoveries are not necessarily equipped or have the ability or interest to move them into clinical trials.

What does work well is a team approach.  You have the innovative scientist who makes the discovery as an important part of that team.  But a lot of what has to be done to translate that into a clinical trial is the preclinical research needed for regulatory submissions — which is not the exciting kind you publish in Nature.  It’s a different skill set than is normal in a discovery lab.  And you need people who understand the disease and where the therapy should best be targeted.  You need people who understand what kind of trial needs to be done to get the right answers.  It takes a lot of people who have complementary expertise who come together in a translational research program and say ‘OK, we think this is potentially going to make a big difference.  This is how we’re going to move it forward in a safe, responsible and effective manner.’ Coincidentally, this is exactly what OIRM is doing, funding these team grants to develop translational teams.

Q: What do you see as OIRM’s role?

A: Ontario is a big player in Canada in this space.  We’re not the whole story but were a big part of the story.  There is tremendous talent.  What OIRM can do is help people understand how to move this forward, how to build these teams.  It’s education: bringing in experts who have had success and helping these teams move forward, helping them build in the areas where they need to build.  It’s not always intuitive.  I see OIRM as a real catalyst.  It also has a role to shepherd these activities in the right direction so there’s the greatest chance of success.

 

 

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25
May 2016
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Dr. Duncan Stewart

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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17
Mar 2016
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Dr. William Stanford

Team shows stem cells reverse osteoporsis in mice

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A single injection of stem cells can reverse age-related osteoporosis in mice, a team of Canadian researchers has shown.

The discovery provides hope of some day developing a treatment for the crippling disease that affects 200 million people worldwide.…

A single injection of stem cells can reverse age-related osteoporosis in mice, a team of Canadian researchers has shown.

The discovery provides hope of some day developing a treatment for the crippling disease that affects 200 million people worldwide.

The Ottawa Hospital’s Dr. William Stanford, senior author of the study published in Stem Cells Translational Medicine, had observed that mice with age-related osteoporosis tend to have low levels of healthy mesenchymal stem cells. He theorized that injecting the diseased animals with mesenchymal stem cells from healthy mice should ease the condition.  Six months after injecting the mice, the team found that osteoporotic bone had given way to healthy, functional bone.

“We had hoped for a general increase in bone health,” co-author Dr. John E. Davies said in a University of Toronto news release. “But the huge surprise was to find that the exquisite inner ‘coral-like’ architecture of the bone structure of the injected animals — which is severely compromised in osteoporosis — was restored to normal.”

About one-quarter of Canadians will suffer a fracture because of osteoporosis at some point in their lives, costing the health-care system more than $2.3 billion each year.  There are few treatment options for the condition.

Mesenchymal stem cells can extracted fairly easily from bone marrow, adipose (fat) tissue, skeletal muscle, umbilical cord blood, placenta, and other sources. A large part of their appeal is they can be transplanted from person to person without being rejected by the body’s immune system. Research also suggests they have anti-inflammatory qualities.

“We stumbled into the bone research field completely by chance a number of years ago, but we felt it was very important to pursue this because age-related osteoporosis takes a huge toll on people and the health-care system,” said Dr. Stanford in an Ottawa Hospital news release. “Obviously we have a lot more work to do, but I’m very excited by the potential that this research could one day help a lot of people.”

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