Fragile X syndrome is an autism spectrum disorder characterized by intellectual disability and behavioral and learning challenges caused by silencing of the gene FMR1.
After Mark Bear’s lab (at Brown University at the time) discovered that the gene’s protein FMRP regulates glutamate receptors and constrains protein synthesis at synapses, he realized that drugs inhibiting excess glutamate signaling, including Arbaclofen, could help patients. In 2012 in Science Translational Medicine, for instance, Bear and colleagues showed encouraging benefits in children.
With the sponsorship of startup company Seaside Therapeutics, the approach reached stage III clinical trials for children, adolescents and adults. The study, published in 2017 in the Journal of Neurodevelopmental Disorders, failed to show significant benefit on the primary endpoints, but encouraging results were obtained with key secondary measures in children. New animal studies continue to suggest the drug may produce benefit in other genetic disorders characterized by intellectual impairment and autism. In 2017, a collaboration between Bear’s Lab and that of Jacqueline Crawley at UC Davis showed significant benefits in mouse models of 16p11.2 deletion syndrome.
To continue the development of Arbaclofen as a treatment for Fragile X syndrome, Bear co-founded a new company in 2020: Allos Pharma.
Above: Dendrites from four experimental mice: wild-type controls, FMR1 knockouts, wild types treated with arbaclofen, FMR1 knockouts treated with arbaclofen.