PureTech snags $11.4M from DOD to test hormone drug in rare brain disease

The Department of Defense has awarded PureTech Health up to $11.4 million to test an experimental therapy for a rare neurodegenerative disease called fragile X-associated tremor ataxia syndrome (FXTAS), the Boston biotech told Endpoints News.

The disease, which PureTech executives say is underdiagnosed, predominantly affects men in their 60s and is characterized by cognitive and motor dysfunction, including tremors that resemble Parkinson’s disease.

Michael Chen

“There is probably a lot of mistaking FXTAS for Parkinson’s disease,” Michael Chen, head of innovation at PureTech, said in an interview. He added that the DOD’s interest in the disease is primarily due to the lack of treatments, not a specific link to soldiers or veterans.

The funds will be used to plan and run a Phase II clinical trial of the biotech’s drug, LYT-300, which is an oral formulation of a natural brain hormone called allopregnanolone. But PureTech CEO Daphne Zohar said her company wasn’t ready to give a timeline for when the trial will start.

FXTAS is related to a neurodevelopmental disorder called fragile X syndrome, which can lead to autism and intellectual disability in children. Both diseases are caused by mutations in the same gene, FMR1, although FXTAS manifests later in life due to differences in those mutations.

FXTAS was first discovered in 2001 by Randi Hagerman at the University of California, Davis. Hagerman led an open-label study showing that weekly intravenous infusions of allopregnanolone showed signs of improving cognition in six men with the disease.

“It was small, but intriguing,” Chen said.

Puretech’s drug, like allopregnanolone, is a positive allosteric modulator of GABAA receptors, the main inhibitory mechanism in the brain. Chen said that “there are some unknowns” as to why the molecules would be helpful in FXTAS, but scientists have some theories.

“Allopregnanolone may have the ability to dampen neuronal excitability and bursting in the brain,” Chen said. “And there is some theory that it may be urging the creation of new neurons.”

Another company, Cambridge, MA-based Sage Therapeutics, won approval in 2019 for an intravenously administered version of the allopregnanolone, marketed as Zulresso, for postpartum depression.

Sage has also developed a chemically modified version of the hormone, administered as a pill and called zuranolone, which could get FDA approval by the end of the week for postpartum depression and major depressive disorder.

Meanwhile, PureTech is testing its drug in anxiety disorders and plans to start a clinical trial in patients with postpartum depression later this year. It will also collaborate with UC Davis’ Hagerman on a placebo-controlled study of its drug in FXTAS.

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biotech
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