A University of Alberta research team has taken the first step toward proving its innovative gene therapy can successfully treat a rare genetic condition called dysferlinopathy that impairs the body’s ability to repair damaged muscles.

In newly published research findings, the team reports it has developed a new antisense oligonucleotide to treat dysferlinopathy. The molecule effectively restored the function of the muscle-repairing protein dysferlin when used to treat cells from dysferlinopathy patients. The molecule triggers a process called “exon skipping” that allows cells to bypass defective genetic instructions and produce the protein needed to rebuild muscle tissue.

Dysferlinopathy is the name used for a group of genetic mutations that interfere with the production of dysferlin. It affects between one in 1,300 and one in 200,000 people, causing progressive muscle weakness that often first shows up in the late teens or early 20s.

“It’s not the most severe form of muscular dystrophy, so many patients live into their 60s and 70s, but they have a lifelong disability and have to use a wheelchair,” says medical genetics professor Toshifumi Yokota, who is the Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair. “It’s a quite devastating disease.”

The findings pave the way for future animal and human studies, Yokota says. 

The Yokota Lab was also behind the development of viltolarsen, a drug approved in the United States and Japan for the treatment of Duchenne muscular dystrophy after clinical trials demonstrated it restored production of another muscle-building protein — dystrophin — and improved muscle function in those patients.

To aid in the development of the new exon-skipping molecules, Yokota collaborated with an international team of experts in computer science, neurology and genetics to develop a machine learning-based tool called eSkip-Finder. Available free for any researcher to use, the tool taps into a large database to identify the optimal genetic sequence to target for exon skipping. 

“Traditionally we had to test many antisense oligonucleotides for efficacy in each cell model, but now the machine learning software can help us predict efficacy,” explains Yokota. “The entire process is more streamlined, and we can more efficiently design antisense oligonucleotides using the new computer tool.” 

In 2024, Yokota was recognized by ScholarGPS as the top contributor worldwide in muscular dystrophy research over the past five years, and the U of A was ranked as the number two academic institution globally in muscular dystrophy research. 

Source: https://www.ualberta.ca/en/folio/2025/03/gene-therapy-shows-promise-for-treating-rare-muscle-disease.html