Some great news out today for parents of kids with Fragile X, a neurological disorder that is also the most common genetic cause of autism: Seaside Therapeutics has begun a Phase III trial of STX209, which could potentially be the first drug available to treat the underlying symptoms of the disorder.
Fragile X, a disorder that, like autism, impacts the way brain cells communicate, is caused by a mutation to the FMR1 gene. People with Fragile X suffer from over-stimulated synapses, creating a kind of signaling noise that prevents them from easily learning through experience.
STX209 is a single-isomer version of the already-approved muscle-relaxant baclofen, a GABA-B receptor agonist. It was identified as a potential treatment for Fragile X after doctors noticed a child who was given the drug to treat a gastrointestinal problem also showed improvements in cognitive function and behavior. Seaside separated out the two isomers and found the efficacy in one isomer and the majority of the negative side effects in the other.
Those following drug development in Fragile X know that both Novartis and Roche have seen promising results in small Phase II trials of compounds that act like a brake on mGluR5, a neurotransmitter receptor that MIT neurologist Mark Bear found to be overstimulated in people with Fragile X. STX209 works by dampening the activity of mGlur5, although the Seaside has another compound in development that works directly on the protein.
Seaside expects to sign up 120 people, ages 12 to 25, with Fragile X, in its Phase III trial, and start a second study for kids ages 5 to 11 in early summer. The trial ages are notable because the Novartis and Roche trials were both conducted on adults ages 18 and up; because the side effect profile of baclofen is well understood, FDA has been willing to allow STX209 to be tested in children.
The continued success of the drug could have implications for the broader autism community. Seaside has already begun testing STX209 in autism with the idea that some of the neurological breakdown could happen along that mGluR5 signalling pathway. And although the trial was small—and was open label, meaning doctor’s knew the kids were getting the drug—the biotech firm was encouraged to see signs of similar improvements in social behavior and cognition as in the Phase II study in Fragile X.
Ultimately, Seaside hopes to develop drugs for other single-gene mutations with links to autism, with the hopes of helping both those patients as well as the broader autism population. The story is still evolving, but it’s encouraging nonetheless to see some good news in a area that is seriously in need of new treatments.
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