Genome Atlantic caught up with Dr. Kym Boycott, a leading Canadian medical geneticist and global expert on rare diseases, to learn more about Canada’s efforts in finding causative genes and developing treatments for rare monogenetic diseases.
Dr. Boycott was in Halifax on Wednesday, March 22 at Genome Atlantic’s invitation to discuss Canada’s Path Forward for Rare Diseases: Discovery to Translation. Her talk focused on the progress and insights that have been attained from using next generation sequencing to pinpoint disease causing genes; the tools and platforms that have enabled these discoveries, and the diagnostic and therapeutic opportunities that have resulted
Gene mutations are known to cause rare diseases like muscular dystrophy and cystic fibrosis, but they are also responsible for thousands of other rare disorders. Although individually rare, collectively these disorders are common, affecting one to three per cent of the population. It is suspected that as many as half of all Canadians with rare disorders are undiagnosed.
Boycott is widely respected for her scientific work and for marshalling Canada’s expertise in the hunt for genes responsible for rare monogenetic diseases. She was instrumental in setting up the highly successful Finding of Rare Disease Genes in Canada Consortium or FORGE Canada Consortium. It focused efforts of 21 Canadian clinical genetics centres, Canadian scientists and international collaborators to identify more than 60 new disease-causing genes using next-generation sequencing.
Today with Dr. Alex Mackenzie, she leads Care4Rare, another pan-Canadian research initiative. The goal now is to improve the diagnosis and treatment of rare diseases. To date, more than 950 rare diseases have been studied and more than 1,500 patients have been provided with a diagnosis. Moreover three experimental therapies are being developed in the lab. She also co-chairs the International Rare Diseases Research Consortium’s Diagnostics Committee.
Based in Ottawa, Boycott is clinical geneticist at Children’s Hospital of Eastern Ontario (CHEO) and senior scientist at the CHEO Research Institute. At the Faculty of Medicine, Univeristy of Ottawa, she is professor of pediatrics and the holder of a tier II research chair in neurogenetics.
Genome Atlantic: What factors do you think have enabled Canada to become a global leader in pinpointing so many genes responsible for rare monogenic diseases?
Dr. Boycott: In Canada we are fortunate to have an engaged and collaborative network of 21 clinical genetic centres scattered across the country. Internationally, this network is recognized as unique in the way it operates. It has been eager to work with scientists, first as part of the FORGE Canada Consortium and now with Care4Rare. Clinician participation has been critical in these efforts because as physicians they understand how discoveries of disease-causing genes can impact the lives of patients and so they have been motivated to move discoveries forward. Relatively speaking, Canadian genetics specialists are a small group, distributed over a wide geography, but they know each other well, network with one another, and are predisposed to working together co-operatively. Those factors have made them quick to respond and go the extra mile to make Canada a global leader, in this area of clinical-scientific endeavour.
Genome Atlantic: How is Care4Rare with its focus on diagnosis and treatment capitalizing on the successful collaboration built by its antecedent, FORGE Canada Consortium (Finding of Rare Disease Genes in Canada) that concentrated on the discovery of disease-causing genes?
Dr. Boycott: Care4Rare continues the gene discovery work of FORGE, using as its foundation the same clinical network. Care4Rare also engages a second group of scientists interested in advancing therapeutic opportunities for patients with rare diseases. Some of the rare diseases that are studied for therapeutic intervention are those that were discovered in either FORGE or Care4Rare.
Genome Atlantic: What are the biggest hurdles to giving physicians the ability to integrate patients’ genomic information with their immediate health-care needs?
Dr. Boycott: For rare diseases we can do this now for many patients. Within the protein coding portion of their genome, we can identify the cause of their rare disease and use that information to guide their management, including optimizing their medications and screening for complications, and providing accurate genetic counseling. More generally, for indications outside of rare diseases, knowledge is the biggest hurdle to integration – there are gaps in what the genomic information means with respect to a person’s health.
Genome Atlantic: Are we any closer to finding a strategy for running networks of small clinical trials for rare disease treatments in ways that will show sufficient efficacy to make therapies more readily available than they are now? If not, what could be done to hasten development of such a strategy?
Dr. Boycott: This is still going slowly, particularly in Canada. The challenges to launching such small clinical trials ¬– the financial support and infrastructure– are significant. Even more importantly, the outcome measures to show efficacy of a new treatment are often difficult to establish. Finally, specific to Canada, our relatively small population and large geographical size mean that the two patients eligible for a particular trial could live at opposite ends of the country in Victoria and St John’s and be unable to travel to take advantage of the opportunity, or the travel could cause financial hardship. Investment in infrastructure for rare disease clinical trialing, such as a hub and spoke type approach, is needed to address these challenges. A hub and spoke approach or a federated system would provide centralized coordination and peripheral sites, thereby allowing patients, wherever they live in Canada, to take part in trials while remaining at home.
Genome Atlantic: Genetic testing of children can raise questions for parents concerned about the potential ramifications beyond health care. Do you think the work of physicians and scientists in your field has been made any easier by the recent passage of the federal bill preventing forced disclosure of the results of genetic testing to health and life insurance companies?
Dr.Boycott: Yes this will make a difference. Sometimes we find something in the genome of a patient that we were not looking for and it is not causing disease now and will not for decades. This type of information will now be protected, which is critical for the patient and their family member