A team of Ottawa doctors is preparing to publish a full report on its breakthrough multiple sclerosis treatment study that has so far eliminated the disease in those treated.
The experimental study began about 13 years ago as a last resort for patients who fail to improve on drug therapy and who suffer severe symptoms of MS. Snippets of the results have been published “here and there,” said, neurologist Dr. Mark Freedman, one of the leads of the program at The Ottawa Hospital, but its never been published in its entirety.
No specific date has been set for its release, but the team’s findings are far from secret. With MS not returning in any of the 24 participants, patient success stories appear in news media across the country. Since the original study’s completion, about another dozen patients have been treated with all of them showing the same results.
Eliminating MS completely and watching patients improve surprised both Freedman and Dr. Harold Atkins, a bone-marrow transplant expert, who started the study. The two originally set out to monitor the development of the disease and find a way to treat it. Their theory was this: Wipe out the entire immune system, reboot it with a transplant of the patient’s own bone marrow and wait for MS to regenerate.
“We thought we might be able to intercept one of the signals that initiates the disease and that would then give us a clue on how to treat it,” Freedman said. He jokes that they “had, in effect, failed because the disease never came back. No one expected to see zero disease activity after the transplant.”
Patients from Vancouver to Newfoundland, who had given up hope, became part of the original 24, including third-year medical student Alex Normandin from Montreal.
The aspiring doctor noticed alarming symptoms of fatigue, numbness and problems with balance and co-ordination. Researchers at the Montreal Neurological Institute confirmed he has a particularly aggressive form of MS, an unpredictable and degenerative disease that affects the central nervous system.
Most patients do not become severely disabled because the illness moves slowly. But in Normandin’s case, the destruction was so fast that doctors expected him to need a wheelchair within months.
Normandin, however, learned of the cutting-edge treatment run by Freedman and Atkins. He became patient No. 19 in the experiment and had his transplant in Ottawa in December 2008.
The procedure has its risks. One patient died in an earlier phase of the trial. It was in 2001 or 2002, Freedman recalled, saying the death was due to the pill form of the drug Busulphan. Used early on in the experiment, the drug attacks the liver twice, both when it enters the body and again when it leaves. But within a year, the team had found that a new intravenous version of the drug improved patient safety tremendously.
Freedman had the task of trying to scare patients by telling them the risks.
“My job was to talk everybody out of it,” he said. “It really is the hardest thing they’ll have to do in their lives. It is a bit of a gamble, but with the fantastic team we have in Ottawa, it’s less of a gamble.”
All participants showed dramatic improvement, and none reported relapses, according to a study on the Freedman-Atkins treatment by a team of MS researchers at the Neuro and the Université de Montréal.
Plus, magnetic resonance imaging (MRI) showed no new lesions in the brain, “no new MS disease activity,” according to findings published in the latest issue of Annals of Neurology.
For Normandin, he’s now a family physician in private practice on the West Island and no longer takes medication for the illness. His fatigue and balance problems continue to diminish daily.
But despite such dramatic results, none of the MS researchers in this study is calling the procedure a cure.
For one thing, it is not known whether the treatment is good at stopping other kinds of MS, explained neurologist Amit Bar-Or of the Montreal Neurological Institute and McGill University and the study’s principal investigator.
Also, bone-marrow stem-cell transplants to treat MS are not approved outside of clinical trials because while the disease itself is not deadly, the procedure is fatal in as much as five per cent of patients.
But Freedman questions the risk rate. He says the five-per-cent figure was from data collected in the 1990s as the team prepared for the experiment. That number has since dropped to about one per cent, he said.
In addition to medical advancements, by comparing the immune responses in patients before and after the treatment, researchers discovered a key biological target for new therapies that might be able to provide similar benefits without the risks associated with knocking out someone’s immune system to facilitate a bone-marrow transplant.
Several studies have already noted that in MS patients, the body’s immune system attacks its own cells. Overactive T cells (a type of white blood cells called lymphocytes) — that are responsible for defending the body against bacteria, viruses and other parasites — can also damage myelin, theprotective insulation covering nerves.
The concept is straightforward, Bar-Or explained. To fight an infection, different types of T cells mount a quick response, then other T cells quickly ratchet back that response, he said. But in auto-immune conditions, including MS, this regulation goes awry and the body attacks itself.
Researchers have zeroed in on a particular subset of T cells, called TH17 cells, that have a substantially diminished function following the experimental transplant. The discovery could help researchers target treatment in MS patients generally.
“We are cautious in not claiming we have figured out all cells responsible for all relapses in all MS patients,” Bar-Or noted. “Keep in mind these patients have very aggressive MS, so maybe TH17 are particularly important in these patients.”
Emerging treatments, however, are already attempting to target TH17 cells, but the story is even more complicated, Bar-Or said.
“We don’t know everything about them (TH17 cells) even in terms of basic immunology. It’s likely that within the TH17 subset there may be particular bad guys ... It would be nice to know which because we need to have these cells some of the time. Getting rid of all of them all of the time, may not be completely safe.”
Both the clinical study at the Ottawa Hospital Multiple Sclerosis Research Unit and biological study in Montreal were funded by the Research Foundation of the Multiple Sclerosis Society of Canada.
Canada has one of the highest rates of MS in the world — affecting about 55,000 to 75,000 people.
Normandin says his illness has been a blessing in disguise, giving him a unique perspective not found in medical text books.
“It changed my whole outlook on life. It definitely affects the way I see patients. I’m more sensitive in how to talk to them and more empathetic dealing with chronic diseases.”
He was once on a career track where the focus was work, but now “life balance” is everything and he is grateful for the treatment that gave him his life back and allowed him to work in a clinic where he can spend as much time as necessary talking to patients.
“Life is great,” he said. “I love to say it.”
Source: The Ottawa Citizen © Copyright (c) The Ottawa Citizen 2013 (18/11/13)