Focus on a Developmental Disorder Opens a Door to Possible Treatments for Other Brain Conditions
In a new, hour-long documentary, South Florida PBS and its 24-hour Health Channel feature vital brain research by area neuroscientists, including Gavin Rumbaugh, Ph.D., of The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology.
The documentary, titled, “The Resilient Brain,” explores the extraordinary complexity of the human brain across the lifespan.
“Through the stories of scientists, patients and families, the film reveals how the brain adapts to trauma, disease and life challenges,” the producers write.
Featured in the documentary is a family affected by a rare brain developmental disorder that’s a focus of Rumbaugh’s research. Carey Noland, Ph.D., and her husband, Hans Schelcht, M.D., have a son affected by mutations to the SYNGAP1 gene, causing developmental disability.
“We knew pretty soon that there was something wrong,” Noland says. “He wasn’t walking or crawling. He wasn’t really hitting any of his milestones. We knew it was something serious, but we didn’t realize just how serious.”
Genetic testing showed a serious SYNGAP1 mutation. Rumbaugh explained the significance.
“SYNGAP1 encodes a critical protein that sits inside the synapse, where it regulates signaling that responds to, say, some new information that you’ve acquired through experience. It allows those synapses to change, to grow and to shrink, almost in real time, to promote storage of that new information,” he says. “By not having full expression of SYNGAP1 in the brain, the brain cannot wire itself properly during development. The outcome is intellectual disability with epilepsy, and high rates of autism.”
Although there are no treatments, Rumbaugh says several academic labs and biopharma companies are developing candidate therapies to boost SYNGAP1 expression. His lab at The Wertheim UF Scripps Institute is designing drug candidates that replenish the missing SYNGAP1 protein.
“We have many drug candidates that boost SYNGAP1 protein levels and activate natural resilience and protection pathways in the brain” says Rumbaugh, who is also a member of UF’s Norman Fixel Institute for Neurological Diseases. “Our approach is unique in that it revolves around small molecules that could be taken as a once per day pill. We are optimistic that human safety trials could begin within five years.”
Early tests in animal models are promising. A medication able to improve brain resilience could benefit other conditions as well, he notes. He is collaborating with Eduardo Candelario-Jalil, Ph.D., on studies of the compounds’ ability to help the brain recover from stroke damage. Candelario-Jalil is co-director of the University of Florida’s Neuroscience Graduate Program and a member of UF’s McKnight Brain Institute.
“With the ability to activate brain resilience pathways, our therapeutic candidates may be effective in other neurological disorders like stroke, Alzheimer’s disease, and even age-related cognitive decline,” Rumbaugh says. “With our collaborators in Gainesville, we have started testing them in these other disease models.”
The documentary, “The Resilient Brain,” can be viewed online via the Health Channel.