Each year in Canada, more than 15,500 people will be diagnosed with epilepsy – 55% of those before the age of ten. In 50-60% of the cases, the cause is unknown. Refractory epilepsy – described as that which cannot be controlled with two or more medications – is especially dangerous, because uncontrolled seizures interfere with normal brain growth, and can make a patient more vulnerable to developing intellectual impairment, autism or psychiatric disorders.
With funding from government and other sources, including a $100,000 gift from the Alva Foundation, Dr. Matthew Farrer, the Canada Excellence Research Chair in Neurogenetics and Translational Neuroscience at UBC and the Dr. Donald Rix BC Leadership Chair in Genetic Medicine, together with partners Dr. Mary Connolly, Director of the Epilepsy Program at BC Children’s Hospital and a Clinical Professor and Head of the UBC Division of Pediatric Neurology, and Michelle Demos, Clinical Assistant Professor in the Department of Pediatrics, is conducting research using whole exome sequencing (WES) to identify the genetic mutations that cause epilepsy.
This research made an enormous difference for toddler Gavin Vadocz, who began having seizures at only three months old. His genetic test showed that his epilepsy was caused by a rare deficiency of a protein called GLUT1, and the treatment for it is simple: a high-fat diet. So instead of pills, he is now eating macadamia nuts and avocado. In another child, a mutation identified through genome sequencing put her at high risk of liver damage, and by changing the drug being used to treat her seizures, her doctor was able to spare that organ from harm.
“In genetic medicine, sometimes called precision medicine or personalized medicine, our goals are to promote rapid innovation and provide accurate, clinically meaningful results,” says Dr. Farrer. “We comprehensively sequence the ‘coding’ genome, the part which encodes proteins, within a week. For most patients and families our approach is much faster and lower in heartache than the current standard of care.”
The results have been impressive: In one third of the epilepsy cases a diagnosis was made with immediate treatment implications. Sequencing the coding genome (alternatively known as whole exome sequencing or WES) was shown to reduce the cost – to less than $5k per patient – and time to obtain results – mean time of 143 days compared to 2,172 days – a remarkable difference to patients and parents anxious for an answer, when every day brings the possibility of greater brain damage from uncontrolled seizures.
With these results, the research team conducted an economic analysis showing the impact of testing the genome of children with epilepsy to provide a better avenue for treatment. The work was highlighted by the American Epilepsy Society in December 2015 and helped lead the American Academy of Neurology to recommend WES as the new ‘standard of care’ in April 2016.
Armed with this knowledge, on April 1, 2017 the BC Ministry of Health approved ‘Sequencing for seizure disorders’ as a comprehensive diagnostic test based on WES. This new health care policy, to provide routine but comprehensive genetic sequencing of children with epilepsy, is a first for Canada. In parallel, Dr. Farrer has created a UBC spin-off, Neurocode Labs Inc. (www.neurocode.com) to provide WES as a clinically-accredited service. Faster, more accurate diagnoses in turn will improve treatments so that the risk of potential long-term brain damage from seizures can be lessened – and over the long term, it will improve quality of life for many more children and adults in BC.
“This is only the beginning, though,” notes Dr. Farrer. “We’ve planned to expand research to develop precision approaches to treating pediatric epilepsy, in partnership with teams in Quebec and Ontario. Investing in treatment at this early stage in the life course will have a ripple effect – preventing the long-term damage caused by seizures and the associated heavy burden these issues place on kids, their families, and the health system.”