Early trial data suggest GT-02287 may ease Parkinson’s symptoms
Phase 1b study shows motor score improvements and biomarker changes
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- GT-02287, an oral Parkinson’s therapy, was associated with modest motor score improvements and reduced levels of the biomarker GluSph in a Phase 1b trial.
- The therapy is designed to boost GCase activity, which is often impaired in Parkinson’s disease and linked to alpha-synuclein buildup.
- Early trial findings support continued clinical development, with a Phase 2 study of GT-02287 planned.
GT-02287, an oral therapy being developed by Gain Therapeutics, was associated with improvements in motor function over three months in people with Parkinson’s disease, including participants both with and without GBA1 mutations.
The findings come from an open-label Phase 1b trial (NCT06732180), which also showed lower levels of glucosylsphingosine (GluSph) in cerebrospinal fluid (CSF) — a fatty molecule that accumulates when glucocerebrosidase (GCase) activity is impaired. CSF is the fluid that surrounds the brain and spinal cord.
Gain Therapeutics has also launched a nine-month extension, allowing participants to remain on GT-02287 for up to one year of total treatment. This extension is expected to conclude later this year. In parallel, the company plans to begin a Phase 2 study of GT-02287 in people with Parkinson’s disease in the second half of the year.
Company highlights biomarker shifts and early motor score signals
“These results mark an important step forward for our program. The observed decrease in GluSph, alongside improvement or stabilization of MDS-UPDRS scores, provides encouraging evidence that our approach is engaging the underlying biology of the disease, suggesting a disease-modifying action. We believe these data support continued clinical development and the potential of our therapy to meaningfully impact disease progression,” Gene Mack, Gain Therapeutics’ president and CEO, said in a company press release.
The results were recently presented during a company-hosted webinar.
Mutations in the GBA1 gene are a known risk factor for Parkinson’s disease. These mutations can lead to a misfolded or dysfunctional GCase, an enzyme that normally helps break down fatty molecules such as GluSph. When GCase function is impaired, toxic clumps of misfolded alpha-synuclein can build up in nerve cells, a hallmark of Parkinson’s.
GT-02287 is a small molecule therapy designed to enter the brain and restore GCase activity, with the goal of reducing the buildup of misfolded alpha-synuclein that damages nerve cells and contributes to Parkinson’s symptoms.
Earlier study showed GT-02287 safely reached the brain
In a Phase 1 clinical trial involving healthy volunteers, GT-02287 was found to be safe and well-tolerated and shown to cross the blood-brain barrier, a protective membrane that surrounds the brain and spinal cord. Treatment with GT-02287 also increased activity of GCase, the enzyme targeted by the therapy.
The Phase 1b study enrolled 21 participants with Parkinson’s disease, including participants with idiopathic disease and those carrying GBA1 mutations. Participants had a mean age of 63.5 years, were mainly men (85.7%), and had diagnosed with Parkinson’s for a mean of three years.
Changes in Parkinson’s symptoms were assessed using the MDS Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) in 15 participants who completed three months of treatment. After three months on GT-02287, MDS-UPDRS Part II scores, which reflect daily living activities, decreased by an average of 0.6 points, while MDS-UPDRS Part III motor scores decreased by an average of 1.6 points, indicating improvements in daily living activities and motor function.
Among participants with elevated baseline cerebrospinal fluid levels of GluSph, treatment with GT-02287 was associated with an average 81% reduction after three months.
“While this study was not designed to assess clinical efficacy, it has been encouraging to see stabilization in MDS-UPDRS scores and to observe anecdotal improvements in specific functional areas such as balance, gait, and sense of smell after 90 days of dosing with GT-02287,” said Michele DeSciscio, MD, lead investigator of the trial.
