A Medicine by Design team is working on reprogramming cells in the brain— a strategy that, as this team’s studies have demonstrated, promotes brain repair in animal models of stroke.
More than 50,000 Canadians have a stroke each year. It’s the third leading cause of death in Canada, and those who survive can have vision problems, memory issues and mobility challenges. Stroke is the leading cause of adult disability in Ontario.
The team’s approach begins with cells called astrocytes. When disease or injury is present in the brain, astrocytes can become toxic, harmful cells that can kill neurons.
A researcher on the team, Maryam Faiz, assistant professor, Department of Surgery, U of T, says the team is developing a gene therapy that can turn astrocytes into healthy neurons again.
“We want to identify subtypes of astrocytes that might limit recovery and turn them to beneficial cell types,” Faiz says, adding that the therapy could apply beyond stroke to all neurodegenerative disease. “Think of it as a bespoke strategy for brain repair.”
Getting the gene therapy to the site if injury in the brain is where Sunnybrook Research Institute researcher Isabelle Aubert, a senior scientist, comes in, using a technique called focus-guided ultrasound, or FUS. This method uses ultrasound to guide a gene therapy, which is placed inside a tool called a viral vector, to the right place and allow it to penetrate the blood-brain barrier.
The team is now working on optimizing the gene therapy before moving towards human testing. Cindi Morshead, a professor in the Department of Surgery at U of T, who leads this team also leads a Pivotal Experiment Fund project to support early-stage translation of the gene therapy for stroke and amyotrophic lateral sclerosis (ALS). The Pivotal Experiment Fund team also collaborates with JoAnne McLaurin, senior scientist at Sunnybrook Research Institute.
This team’s success has also led to a New Frontiers in Research Fund grant in the Transformation stream, led by another investigator on the project, Carol Schuurmans, senior scientist at Sunnybrook Research Institute, a prestigious award that will integrate a 24-member international team to rapidly accelerate this therapy.