THE ROBERT CONLON RESEARCH GRANT RECIPIENT
Dr. Peter Carlen, MD, FRCP(C)
Neurologist, Toronto Western Hospital (UHN)
Professor in Medicine (Neurology), Physiology, and Biomedical Engineering at the University of Toronto.
Senior Scientist, University Health Network
Grant Project: Mitochondrial Medicine for Epilepsy: a formulation of multiple antioxidants to treat epilepsy and comorbidities
Project Summary:
A brief, lay-oriented description of the rationale for this project and how it will be carried out. Include key goals,
deliverables, and the anticipated impact on people living with epilepsy. (maximum 300 words)
Up to 1% of the population have epilepsy, and one third are drug-resistant. Many patients experience significant
medication-related side effects, and epilepsy-related comorbidities including cognitive impairment, depression, and
reduced quality of life. There remains a critical unmet need for therapies that address underlying disease
mechanisms while remaining safe, accessible, and affordable.
Mitochondrial dysfunction is increasingly recognized as central to seizure generation and epilepsy-related
comorbidities. We are demonstrating that multiple-antioxidant (MAO) therapy greatly improves epilepsy control along with enhancing mitochondrial health.
The overarching goal is to develop a safe, cost-effective, non-toxic formulation of multiple antioxidants (MAO)
as a therapy for patients with drug-resistant epilepsy, with the potential to reduce seizure burden and improve
epilepsy-related comorbidities.
Aims
Aims 1 & 2. Using mouse models of spontaneous recurrent seizures in vivo (1) and in vitro (2), we will determine
whether MAO administration reduces seizure generation while simultaneously measuring changes in
mitochondrial/metabolic pathways, using metabolomics - the comprehensive, measurement and study of
metabolites, the small-molecule substrates, intermediates, and products of cellular metabolism.
Aim 3 (Clinical probing study): We will assess mitochondrial and metabolic signatures using metabolomic analyses in
individuals with drug-resistant epilepsy, drug-controlled epilepsy, and non-epileptic controls.
The above experiments are designed to lay the foundations for a clinical trial of an optimized baseline MAO therapy
for drug resistant epilepsy patients, and in the future, to personalize MAO mixtures depending on the metabolomic
profiles of an individual patient.
This work will inform the rational design of an optimized MAO formulation, supporting future clinical trials.
Importantly, most antioxidants are well-tolerated, non-toxic at therapeutic doses, and inexpensive compared to
conventional drug development pipelines. As such, this research has the potential to yield a cost-effective, scalable
therapy that could reduce seizure burden and improve comorbidities for people living with epilepsy, particularly
those with drug-resistant disease.