2024 TRANSLATIONAL GRANT AWARD WINNER

Dr. David Dyment

Clinical Investigator, CHEO Research Institute

Associate Professor at the University of Ottawa

Grant Project: Translational Lipidomics:Treatment of a novel mouse model of progressive myoclonic epilepsy with repurposed drugs and recombinant enzyme

Project Summary: My colleague Dr. Steffany Bennet, and I research therapies for spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). This is a rare disorder of the lysosome that results in muscle weakness and difficult-to-treat seizures. SMA-PME progresses quickly, and individuals with the condition often die in their teens or early 20s. In the beginning of my career I diagnosed a child with SMA-PME and the lack of any effective treatment for her has motivated me, and Dr. Bennett, to research and develop new therapies for this devastating disorder.

SMA-PME is due to the impaired functioning of an enzyme known as acid ceramidase. Without this enzyme, the levels of ceramide in cells increases and this results in the symptoms associated with SMA-PME. Metabolic and lysosomal storage disorders, like SMA-PME, are complex in nature and our research studies into finding potential therapies has taken many years; however, recently we have developed several promising avenues for therapy including the re-purposing of FDA-approved drugs and introducing the acid ceramidase enzyme to normalize affected cells. Critical to our work is the development of a mouse that mimics the seizures seen in SMA-PME. The mouse is unique and is based on the first genetic changes seen in the first Canadian patient diagnosed with SMA-PME.

Thanks to Epilepsy-Canada, we will be able to test these potential treatments in the mouse model, which is a critical step before starting human studies. Insights gained in our research will be beneficial not just for SMA-PME but for other progressive myoclonic epilepsies. 

I am a medical geneticist at the Neurogenetics Clinic at the Children’s Hospital of Eastern Ontario with a focus in the rare forms of genetic epilepsy. I completed a DPhil in genetic research at the University of Oxford and an MSc in medical genetics at the University of British Columbia. My collaborator in research is Dr. Steffany Bennett. She completed her doctoral training at the University of Ottawa and post-doctoral studies at the W. Alton Cell Science Centre and Harvard Medical School.  She is the University’s Research Chair in Neurolipidomics and full professor in the Department of Biochemistry, Microbiology, and Immunology at the University of Ottawa.