Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Multiple Sclerosis (MS) is a chronic, degenerative disease of the central nervous system and is the most common cause of neurological disability in young adults in the Western world with approximately 75,000 Canadians affected. British Columbia and Canada as a whole have some of the highest prevalence rates of MS in the world. Immunomodulatory drugs (IMDs), such as beta interferons (IFNB), are the most prescribed treatments for MS cases in Canada with an annual cost of around $188 million and a direct drug cost of $18 to 22,000 per patient per year. However, their effectiveness is considered moderate, and they possess many adverse drug reactions (ADRs) ranging from mild to fatal, including liver failure. There have been several case reports of liver failure and death associated with IFNB treatment of MS patients. While the long term consequences are unknown of developing liver injury associated with IFNB, the few liver biopsies that have been published have shown liver necrosis and fibrosis such that long term effects are possible. We are unaware of any other group successfully using genotypic methods to prevent or predict ADRs in MS patients; we aim to do so, with the ultimate goal of identifying robust prognostic markers exploitable for 'personalized medicine'. Cases and control samples will be analyzed to identify genetic variants associated with susceptibility to serious drug reactions to MS IMD treatments via genome wide panels developed by the Canadian Pharmacogenomics Network for Drug Safety. Importantly, these associations will be of clinical diagnostic significance, by focusing on identifying genetic markers of clinical diagnostic utility with high odds ratios. The proposed research can improve personal and population health by identifying MS patients at a greater risk of developing serious ADRs to MS IMDs. This study will also benefit Canadian health delivery systems via facilitating personalized treatment choices and drug monitoring.