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.