Pharmacogenomic studies in Multiple Sclerosis

Multiple sclerosis, an autoimmune, neurodegenerative condition, is the most common cause of non-traumatic neurological disability in young adults. At present 14immunomodulatory or immunosuppressive therapies with varying levels of treatment efficacy are approved for the treatment of MS in Australia. All drugs have been shown to reduce relapse rates in clinical trials, and some have also been shown to have disability progression and MRI benefits. However, individuals are known to have variable responses to these therapies, and can be classed as treatment responders, intermediate responders and non-responders. This project aims to identify genetic markers of treatment response to various MS disease-modifying therapies. This project will involve both wet lab and dry lab work. The student will participate in performing DNA extractions from human blood. The student will also utilise genetic data that is linked to a global observational cohort to identify genetic markers of treatment response and non-response. This will involve both bioinformatic and machine learning approaches. Outcomes and impact: The identification of genetic predictors of MS treatment response will have a significant impact on MS clinical management, and treatment decision making. It will allow the stratification of patients for therapeutic choice, reduce treatment trial-and-error and prolong patient quality of life. Research Environment: The proposed project will be undertaken using the MSBase Registry, an international, prospective, observational MS cohort study. It currently contains over 75,000 longitudinal patient records, with over 350,000-patient years of follow-up. Within the MSBase observational cohort study, we have formed a special interest group to examine genetic factors associated with disease outcome and treatment response. This group comprises 12 centres that have the capacity to undertake genetic studies. Here, our cohort comprises 8,574 patients, with 80,000 patient-years of follow-up with visits occurring on average every 6 months, thus allowing for accurate stratification of treatment responders and non-responders.