NEW INVESTIGATOR AWARD 2021 WINNER
Dr. Colin Josephson, Assistant Professor of Neurology and Community Health Sciences, O'Brien Institute for Public Health, Centre for Health Informatics & Hotchkiss Brain Institute - University of Calgary
Grant Project: Leveraging a multisource precision medicine and advanced analytics to reduce the burden of pharmacoresistant epilepsy
Grant Awarded: $50,000
Project Summary:
“It is currently extremely challenging to predict which patients will respond to a particular antiseizure medication (ASM). Currently, we have over 20 ASMs and health care workers strongly rely on factors other than predicted effectiveness, such as side-effect profiles, dosing schedules, and the patient’s medical history, when selecting a drug). This may expose people to unnecessary delays in achieving seizure freedom, elevated risks of harm from ongoing seizures, and the psychosocial consequences of uncontrolled epilepsy. We propose that precision medicine offers a new strategy to remedy the conventional ‘trial and error’ approach. Precision medicine accounts for an individual’s unique collection of clinical, physiologic, genetic, and sociodemographic characteristics to provide patient-specific predictions on how their own disease will progress and how they will respond to therapy. Previously, these types of analyses were unrealistic due to heavy computational demands. Now, with the advent of machine learning and high-performance computing, we can evaluate how a person’s own unique physiology helps predict their disease pattern.
To this end, we have identified 400 patients from which we will extract raw signal data from patient brain waves (electroencephalography) and imaging (MRI images) from the first tests they underwent during the course of their care. These data will be combined with their clinical and genetic information to model who will respond to an ASM and who will not. We have assembled a multidisciplinary team with extensive experience in large clinical datasets, machine learning and computational neurosciences, biostatistics, and genetics ensuring we are well positioned to produce robust, clinically accessible results. The models generated from this study will be ready for immediate deployment in external validation studies to predict each patient’s individual response to ASMs. We already lead a national collaborative network, the Canadian Observational Study of Epilepsy (CANOE). Epilepsy centres participating in this network will be able to deploy our models and software and these data will be used to inform additional future efforts to design ASM-specific models.
I was drawn to epilepsy given we have made significant strides in the understanding of most organ systems, yet the brain remains a ‘black box’. The characteristics of seizures have led to incredible breakthroughs in understanding the circuitry of the brain, meaning not only can we help people with epilepsy, but we can also begin to better understand the human condition. Additionally, epilepsy is a complex disease that transcends just seizures. Although seizures are required for the diagnosis, the disease is also characterised by the associated medical, psychological, and socioeconomic consequences of the condition. This was a major impetus in pursuing a career in epilepsy, since addressing these issues allows one the satisfaction of getting to know their patients as a person and not simply a disease. Our project will promote this by using personal data to guide individual level prescriptions, optimising the effectiveness of prescriptions all whilst minimising the risk of adverse effects, which will lead to earlier seizure control and improved quality of life. This precision medicine paradigm, once refined, can be applied to all aspects of epilepsy care to better mange comorbid disease, improve mental health, and optimise socioeconomic function.”