The Canadian Institutes for Health Research, a federal government agency based in Ottawa, has awarded genetics professor Kessen Patten C$627,300 to study the mechanisms involved in spinal muscular atrophy (SMA).
The leading genetic cause of infant mortality, SMA is a neuromuscular disease that involves the death of lower motor neurons — the nerve cells in the spinal cord that activate muscle cells. This leads to muscle weakness and eventually atrophy.
The connections between nerve cells and muscles occur at sites called synapses. Learning how they become dysfunctional is crucial to advancing understanding of SMA. However, it is difficult to study synapses in mammals since they occur within the body’s tissues.
Patten focuses his research primarily on the early stages of SMA onset. He studies SMA-associated genes in zebrafish to understand how they cause abnormalities in synapses. Specifically, they look at genetic causes of pediatric musculoskeletal conditions, genetic mechanisms of neuronal survival in neurodegenerative diseases, zebrafish models of human neurological diseases and drug discovery.
Zebrafish are used in research on human diseases for several reasons. They’re cheaper than mice and reach adulthood more quickly after birth. They share 70 percent of the same genes with humans; in fact, 84 percent of the genes linked to human disease have a related gene in zebrafish.
They also share conserved neurochemistry and broad brain organization with mice, the most common mammal used in neuroscience research. Other advantages include the zebrafish’s small size, conservation of the neuropeptide pool, linear organization of brain regions, structural accessibility of internal nuclei and optical clarity (since zebrafish brains are translucent).
Patten has published several manuscripts on his discoveries and received multiple awards, including a grant from ALS Canada and Brain Canada to study the genetic mechanisms behind amyotrophic lateral sclerosis (ALS) and to translate his findings into the clinic. His zebrafish models of human disease have already been used to develop a high-throughput method for drug discovery, leading to the identification of pimozide as a lead compound in a translational pipeline for ALS treatment.