A research team at the University of Alberta has taken a significant step toward advancing gene therapy as a potential treatment for dysferlinopathy, a rare genetic condition that impairs the body’s ability to repair damaged muscles.
In recently published research, the team unveiled the development of a novel antisense oligonucleotide designed to treat dysferlinopathy. This molecule successfully restored the function of dysferlin, a muscle-repairing protein, when tested on cells derived from patients with the condition. The therapy works by initiating a process known as “exon skipping,” which enables cells to bypass defective genetic instructions and produce the necessary protein to repair muscle tissue.
Dysferlinopathy is a group of genetic disorders that disrupt the production of dysferlin. Affecting between one in 1,300 and one in 200,000 individuals, the disease causes progressive muscle weakness, often first appearing in late adolescence or early adulthood. Although it is less severe than other forms of muscular dystrophy, dysferlinopathy typically results in lifelong disability, with many patients requiring a wheelchair as they age, though many live into their 60s and 70s.
Professor Toshifumi Yokota, a medical genetics expert and holder of the Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair, described the disease as “quite devastating” for those affected. The new findings are a critical milestone, Yokota says, paving the way for future animal and human clinical trials.
Yokota’s lab previously contributed to the development of viltolarsen, a drug approved in the U.S. and Japan for the treatment of Duchenne muscular dystrophy. This drug demonstrated success in restoring dystrophin, another protein crucial for muscle function, and improving muscle strength in patients with the condition.
In the latest study, Yokota collaborated with a global team of experts in computer science, neurology, and genetics to develop a machine learning-based tool, eSkip-Finder. This tool, which is freely available to researchers, uses a large genetic database to predict the most effective genetic sequences for exon skipping.
“Traditionally, we would have to test numerous antisense oligonucleotides in each cell model,” said Yokota. “Now, the machine learning software helps us predict which ones will be most effective, making the process more efficient and streamlined.”
Yokota’s groundbreaking work was recently recognized by ScholarGPS, which named him the top global contributor to muscular dystrophy research over the past five years. Additionally, the University of Alberta was ranked second worldwide in this field.
“This ranking means a lot to us,” Yokota said. “We are grateful to our supporters, team members, and colleagues for their contributions.”
In addition to his academic achievements, Yokota co-founded OligomicsTx, a company focused on translating genetic discoveries into clinical treatments for neuromuscular diseases. The company aims to develop novel therapeutics using technologies such as antisense oligonucleotides and CRISPR genome editing to ultimately cure muscular dystrophy and help patients regain mobility.
Yokota credited the success of the research to the patients who donated cells and the generous support of donors to the Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair Fund. The project was also funded by a grant from the Canada Foundation for Innovation, which helped secure specialized equipment for analyzing cell membranes.
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