FRAXA Supporting Work Into Drug Repurposing to Treat Depression

The FRAXA Research Foundation is supporting a project to identify available medicines that might be repurposed to treat major depressive disorder (MDD) in people with fragile X syndrome.

Depression occurs frequently among people with autism spectrum disorders (ASD), of which fragile X is the most common genetic cause. However, recent research in a mouse model of fragile X suggested that standard antidepressant therapies need the FMRP protein to work. People with fragile X have little to no FMRP.

“So what works in a person who suffers from major depressive disorder is likely not to work for a person with fragile X or maybe even other types of autism,” Kimberly F. Raab-Graham, PhD, an associate professor of physiology and pharmacology at Wake Forest School of Medicine and the proposed study’s principal investigator, said in an interview with the foundation. Raab-Graham was also the senior author of the antidepressant study in mice.

Caretakers of those with fragile X report mood and depression as priorities for developing treatments.

MDD, also called major depression, is a disorder characterized by persistent feelings of depression and a loss of interest in many activities.

Raab-Graham’s research indicates that FMRP helps standard antidepressants work by increasing brain cell connections and strengthening communication between those cells. Without the FMRP protein present, these therapies may have no way to work.

Raab-Graham and Chelcie Heaney, PhD, a post-doctoral researcher in her lab, will use computational methods to predict which FDA-approved drugs may be capable of boosting these brain cell connections without FMRP. They will then test the candidate therapies identified in a fragile X mouse model.

This approach, known as drug repurposing or drug repositioning, is used to expand the number of treatments available for a given condition by finding new uses for approved medications. If a likely candidate is seen, its clinical testing for effectiveness in fragile X  might move through a trial more quickly, as the safety profile of approved drugs is known.

Viagra (sildenafil) is a classic example of drug repurposing. Originally developed to treat high blood pressure and chest pain associated with narrowed blood vessels, its now better-known use as an erectile dysfunction treatment was a side effect. This secondary use won regulatory approval two years after the compound, sildenafil, was patented — an extremely short time compared to that of a novel drug’s development and approval process.

Through their computational approach, Raab-Graham and Heaney hope to develop a rapid screening method that will shorten the amount of time needed to move potential medications from the lab into the clinic, a process often referred to as “bench-to-bedside.”

The FRAXA Research Foundation is supporting this effort with a $90,000 grant.

“It’s allowing me to really focus in on this question of how this one little protein, FMRP, can have such a large impact, not only on just how your cells work but also how that impacts behavior,” Heaney said.