Clinician scientist armed with stem cells gives MS patients their lives back
In 2001, Dr. Harold Atkins, an OIRM scientist, enrolled the first patients in a clinical trial for an aggressive, untested treatment for multiple sclerosis. A short time later, patient number five failed — by recovering far beyond what anyone had imagined. Now, Dr. Atkins is being recognized for his pioneering efforts with the Till & McCulloch Award.
As clinical trials go, early phases are not about cures, or even treatments. Failure is common and meeting the safety thresholds is often all one can hope for. Learning that your experimental treatment goes way beyond your wildest dreams is akin to winning the lottery.
Dr. Harold (Harry) Atkins knows what this is like. The multiple sclerosis (MS) trial he launched in 2001 with colleague Dr. Mark Freedman has consistently delivered more than the pair dared to hope. But although the results may have been surprising, the road to get there was peppered with just the right amount of methodology, instinct, and the guidance of a really good mentor.
Atkins’ interest in using stem cells as a therapy dates back to the earliest days of his medical training.
As a medical student, Atkins took an elective where he was placed into a research laboratory studying bone marrow. “We would take samples from a patient and grow them in the lab, and at the same time we would do these new things called bone marrow transplants, and it all seemed really cool and a great way to combine science and medicine together,” he explains, “and that’s really how I came to be in the field I’m in.”
After finishing medical school at the University of Ottawa, Atkins moved to Toronto for a research fellowship in experimental hematology at the Ontario Cancer Institute. One of the factors pulling him to Toronto was Dr. Ernest McCulloch — one half of the scientist duo responsible for first demonstrating the existence of stem cells, and for whom the eponymous award has been named — who was working at the Ontario Cancer Institute at the time.
Atkins had the opportunity to work alongside and learn from McCulloch — a legend in stem cell biology and Atkins’ mind.
“My training started in the ’80s, and so you always heard about Till and McCulloch,” explains Atkins. “The reason I went to Toronto was because of a meeting with Dr. McCulloch.” Over his time spent in Toronto, Atkins got to know McCulloch personally. “I sat in with his lab meetings over time and helped. We talked about leukemia care,” he recalls.
At this year’s Till and McCulloch meetings, Atkins will be awarded the annual Till & McCulloch Award, in recognition of his innovative work developing a stem cell therapy for MS.
His early career encounters with McCulloch have put the award into perspective for Atkins, who is still having difficulty accepting that he was chosen for such an honour. “They’re such heroes to me, and you know, it’s hard to compare what I’ve done to the amazing thing that they figured out. And so, it’s kind of like a little bit of a dream because of that.”
So, Atkins completed his research training in the city that was arguably the heart of stem cell research at the time, and worked in the same circles as one of the scientists who earned the city that reputation. When he returned to Ottawa in the mid-90s, then, it’s no surprise he continued exploring the potential of stem cell transplantation.
Atkins, however, is trained as both a physician and a scientist — a position that he argues obligates himself to explore beyond the basic biology of stem cells. “If you are a biomedical scientist who is also a physician, you shouldn’t limit yourself just to looking at test tube reactions,” he says. “And so I thought that it’s important to know how to do clinical research as well.”
Specifically, he was interested in testing if the current methods of stem cell transplantation used to treat leukemia could be co-opted into treating auto-immune disorders. “When I started in Ottawa, I was thinking, ‘Okay, we can change an immune system from a recipient to that of a donor using a bone marrow transplant’, and I wondered if it was something that could be used to treat other autoimmune diseases — we would wipe out the immune system and replace it,” says Atkins.
In auto-immune diseases, the patient’s immune system can’t distinguish its own tissue from foreign tissue. This causes the immune system to attack and often destroy healthy tissue, and underlies the pathogenesis of diseases ranging from diabetes to lupus. Atkins speculated that wiping out the existing defective immune system and re-establishing it to develop anew with a stem cell transplant might eliminate the self-destructive behaviour.
When he arrived at The Ottawa Hospital, he learned that many of his colleagues were making similar speculations but were focused on the autoimmune disease rheumatoid arthritis. Atkins, however, had different plans.
He met with neurologist Dr. Mark Freedman, also at The Ottawa Hospital, and together they decided the autoimmune disorder MS would be a better disease to test their nascent theory on. The disease itself urged for an innovation in care. “The MS doctors were quite aggressive here; they were very interested in trying to prevent their patients from being disabled. And at that time there were just a few drugs that were able to treat MS or hold MS at bay for any period of time.”
And so, in August of 2001, Atkins and Freedman collected a small group of patients, and started a clinical trial.
The goal of the trial was simple — Atkins wanted to restart the immune system and stop the progression of the disease. He wasn’t aiming to cure these patients, just prevent them from getting any worse.
The treatment Atkins developed, while innovative, was not exactly delicate. Each patient had their own hematopoietic stem cells harvested, followed by an intense regiment of chemotherapy designed to obliterate their existing immune cells. After chemotherapy, the stem cells were delivered back into their bone marrow. The treatment itself was risky, with each patient facing a 1-in-10 chance of dying. For this reason, Atkins only enrolled patients with aggressive and advanced symptoms of MS who had largely failed to respond to conventional therapies — patients for whom this therapy was seen as a last resort.
One such patient, patient number five, was Jennifer Molson.
In 2001 Molson was living full-time at the Ottawa Hospital Rehabilitation Centre. Molson, then only in her 20s, required 24-hour care, and relied on a wheelchair to get around. Molson joined the trial in 2002. To the surprise of both Atkins and Molson herself, four years later, she was driving herself to work.
“It’s the study that failed, right? The best thing they were hoping for was stability and instead the people were getting better,” jokes Molson.
“That was kind of like science fiction — the patients came in and started to tell us that they were walking better, and you know, some of these were not subtle things,” says Atkins. “They got [much] better, and that was really just so astounding.”
It turned out that a subset of the patients enrolled in Atkins trial retained some ability to repair the damage done from the disease. Their new immune systems no longer attacked their own tissue, and their bodies had repaired a great deal of the previous damage — taking patients like Molson from being wheelchair bound, and giving them back the life they had before MS.
Sixteen years later, the results of the clinical trial were published in the journal The Lancet, one of the world’s most prestigious medical journals. The trial represented the first treatment to lastingly halt the progression of MS. Dr. Atkins pioneered a stem-cell based therapy that continues to change the lives of patients suffering from MS. He has since expanded this clinical trial to other rare autoimmune diseases such as stiff person syndrome, myasthenia gravis and scleroderma.
Molson, who is now a colleague of Atkins at the Ottawa Hospital Research Institute, cannot understate the impact Atkins’ work has had on her life, and the lives of many patients like her. “It was ten years ago, when they opened the stem cell research floor at the OHRI. Dr. Atkins and I were there and I said, ‘you know, if it wasn’t for you I wouldn’t be here today’.”
To which Dr. Atkins coyly responded, “Yes you would… You’d just be in a wheelchair.”
Editor’s note: a correction was made after publication, changing patient number from six to five.
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