A team of researchers at the University of Alberta is offering hope to people with a rare genetic disorder that progressively turns soft tissue like muscles and tendons into bone.
In newly published research, the team used a new experimental RNA-based approach to develop a “gapmer” molecule that can selectively target the disease-causing mutations while sparing normal genes, thus reducing unwanted side-effects.
“This research is significant because it addresses a major unmet need in fibrodysplasia ossificans progressiva (FOP), an ultra-rare and devastating disorder with very limited treatment options,” explains principal investigator Dr. Toshifumi Yokota, Distinguished University Professor of medical genetics.
The disease affects one in a million people, according to the Canadian FOP Network, with symptoms beginning in early childhood.
In human cell and mouse studies, the researchers further demonstrated that a small chemical modification to their molecule improved selectivity for the disease-causing RNA transcript, reduced abnormal bone-forming signals, increased delivery of the drug to muscles and tendons, and lowered signs of liver and kidney stress.
“These findings suggest a promising new direction for more precise and potentially safer RNA therapeutics for FOP,” says Yokota, who holds the Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair.
The research was funded by the BC Children’s Hospital Foundation, theRare Disease Foundation, the Canadian FOP Network, the Canadian Institutes of Health Research, the Gilbert K. Winter Fund, the Stollery Children's Hospital Foundation through the Women and Children’s Health Research Institute, and the International FOP Association.