GT-02287 boosts enzyme activity in Parkinson’s brain: Trial data
Developer Gain Therapeutics to review results in January webinar
- GT-02287 boosts GCase enzyme activity in Parkinson's brains.
- Parkinson's involves impaired GCase, high GluSph, and alpha-synuclein buildup.
- Trial data shows GT-02287 is safe, reduces GluSph, and improves motor symptoms.
GT-02287, an oral therapy being developed by Gain Therapeutics, can increase glucocerebrosidase (GCase) enzyme activity in the brains of people with Parkinson’s disease.
Results from a Phase 1b trial (NCT06732180) show that approximately three months of treatment with GT-02287 was safe and led to a robust reduction in cerebrospinal fluid (CSF) levels of glucosylsphingosine (GluSph), a substrate of GCase. Cerebrospinal fluid surrounds and protects the brain and spinal cord.
High levels of GluSph — a sign that the GCase enzyme is not working properly — can promote the buildup of alpha-synuclein, a hallmark of Parkinson’s, and disrupt energy production and other essential processes inside nerve cells.
Gain said it will review the findings on a Jan. 6, 2026, “key opinion leader” webinar featuring Roy Alcalay, MD, chief of Tel Aviv Sourasky Medical Center’s movement disorders division, and Harvard University professor Peter Lansbury, PhD. The event will include a presentation of the data followed by a live question-and-answer session. Registration is now available, with additional details to be announced closer to the event.
“To our knowledge, GT-02287 is the first GCase modulator to demonstrate a reduction of GluSph in CSF in people with [Parkinson’s], providing downstream evidence of GCase enhancement in the brain,” Gene Mack, Gain’s president and CEO, said in a company press release. “We believe that reduction in brain GluSph levels will have a direct impact on neuronal health and translate to clinically observable improvements.”
Trial extension launched
Gain has launched a nine-month extension of the trial, with 15 of the 21 patients enrolled in the first part agreeing to continue treatment. The company anticipates completing the extension part of the trial in September 2026.
Mutations in the GBA1 gene, which encodes the GCase enzyme responsible for breaking down fatty molecules, are among the most common genetic causes of Parkinson’s. When GCase function is impaired, toxic substances accumulate, including misfolded proteins such as alpha-synuclein.
GT-02287 is a small oral molecule designed to enter the brain and bind to and restore the activity of GCase, preventing misfolded alpha-synuclein from forming toxic clumps and contributing to Parkinson’s symptoms.
In preclinical models of Parkinson’s, GT-02287 restored GCase activity and reduced aggregated alpha-synuclein, neuroinflammation, nerve cell loss, and blood levels of neurofilament light chain, a biomarker of neurodegeneration. In animal models of both GBA1-associated and idiopathic (or of unknown cause) Parkinson’s, treatment with GT-02287 also improved motor function and gait deficits.
In a Phase 1 clinical trial in healthy volunteers, GT-02287 was found to be safe and well tolerated and reached expected levels in the CSF, meaning it can effectively enter the brain. GT-02287 also increased GCase activity among those receiving the treatment at clinically relevant doses.
The Phase 1b trial is testing GT-02287 in Parkinson’s patients in Australia who have either idiopathic disease or carry mutations in GBA1.
Interim data from the trial demonstrated that GT-02287 was safe and well tolerated, easing motor symptoms and helping people with Parkinson’s disease, with or without mutations in the GBA1 gene, to maintain daily activities over three months.
“We look forward to presenting longer follow-up from the study at the AD/PD conference in March 2026, observing the effect of GT-02287 treatment on MDS-UPDRS scores in the participants who continued in the nine-month extension, and determining the durability of some of the anecdotal signs of early functional improvement,” Mack said.
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