Dr. Bernard Bryce of The Neuro (Montreal Neurological Institute-Hospital) at McGill University
Suffering from a serious neurodegenerative disease is difficult, but when it’s impossible to know what the disease is, the stress and frustration become much greater.
For Dr. Bernard Bryce, a clinician-scientist at The Neuro (Montreal Neurological Institute-Hospital) at McGill University, being able to give patients a definitive diagnosis is one of the most rewarding parts of his job.
Recently, Dr. Brace led an international study that discovered the genetic cause of a common late-onset ataxia, a disease that gradually reduces a person’s balance, often to the point where they need walking aids. One to three people in 100,000 worldwide will develop late-onset ataxia.
Published in the Jan. 12 issue of The New England Journal of Medicine, the study found a disease-causing mutation in the FGF14 gene. By analyzing the gene in ataxia patients both in Quebec and abroad, Dr. Brais’ team found that the mutation is one of the most common genetic causes of late-onset ataxia described to date. This explained 61 percent of the cases in Quebec and between 10-18 percent in the German, Australian and Indian patient groups.
Now, previously undiagnosed patients can be tested for this mutation, possibly ending their search for answers.
“For the past 20 years, I have promised late-onset ataxia patients that I would work hard to find the cause of their familial ataxia,” says Dr. Bryce. “Finally informing them that not only have we found the cause of their disease, but that it is probably the most common cause of ataxia in adults in Quebec and that it will soon lead to a therapeutic trial is one of the most rewarding experiences I’ve had I am like a researcher and a treating doctor.’
What’s more, it opens up the possibility of a clinical trial that could alleviate some of the symptoms. One drug in particular is showing promise. 4-Aminopyridine is a drug already approved by Health Canada for other neurological conditions. It has already shown positive results in a small group of patients with an FGF14 mutation.
“Our findings open the door to a clinical trial of this drug in these patients,” says Dr. Bryce. “This is great news for patients in Canada and around the world.”
The repeat sequence of the FGF14 mutation is identical to that in a gene called FXN, which causes Friedreich’s ataxia, the most common form of autosomal recessive ataxia worldwide. Because of this similarity, some of the new treatments being developed for Friedreich’s ataxia could possibly be used to treat patients with FGF14.
Inspired by those who came before
Like many physicians, Dr. Bryce chose his specialty through the influence of mentors. The first thing that turned him on to neurology was meeting the late William Findel, former director of Neuro, while attending medical school. They shared a love of history, something that came in handy later in Dr. Brace’s career when he was tracing the origins of founder-caused diseases in Quebec families.
The second factor is that his mother has a neurological disease.
“When I visited her at The Neuro, I saw how the neurologists were treating her case. At that point I said to myself, “This is what I want to do. This major really interests me.”
A third influence that steered him toward neurology was Dr. George Carpati, a neurologist specializing in neuromuscular diseases.
“Through him, I learned about the opportunity to do neuromuscular research at The Neuro.”
Finally, his former McGill professor, Dr. Charles Scriver, one of the world’s top geneticists, convinced him that he could make a career out of the story of hereditary neurological diseases in Quebec.
“My interests eventually aligned to set me on my path. I became a neurogeneticist and started working in the field of neurogenetics after my PhD with Dr. Guy A. Rouleau, a discipline that has evolved so much and transformed modern neuroscience.”
“This was in the 1980s, a time of great change in genetic technology. We were at a point where studying the French-speaking population of Quebec, because of the founder effect, could potentially lead to major advances in genetics, in particular by accelerating the discovery of new disease genes.
The initial discovery of the FGF14 mutation was possible because it is much more common in Quebec, where it corresponds to founder disease. Its higher incidence makes it a more significant health problem in the province. The neuroscience-led team’s goals are to better understand how the genetic error leads to disease and to give Quebec’s large number of cases access to new therapies.
This work would not be possible without the support of the Montreal-based Fondation Groupe Monaco, the Montreal General Hospital Foundation and many national agencies.
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