Phase 1b results for GT-02287 point to biological impact in Parkinson’s, strengthening the case for disease-modifying approaches.
Progress in Parkinson’s disease has been judged largely by visible symptoms. Tremors, rigidity, gait changes have been the bellwethers for decades. Beneath those outward signs is a quieter story, one unfolding at the cellular level, where aging neurons struggle to clear toxic buildup and maintain energy balance. New data from AI-powered biotech Gain Therapeutics suggest that the story may finally be measurable and possibly alterable.
In its latest update from a Phase 1b clinical study, Gain Therapeutics reports biomarker evidence that its lead candidate, GT-02287, engages the underlying biology of Parkinson’s disease rather than merely addressing surface-level symptoms [1]. For a field long marked by stalled disease-modifying efforts, the findings offer a cautiously optimistic signal.
The key finding centers on glucosylsphingosine (GluSph), a fatty substance that builds up when an important brain enzyme called glucocerebrosidase (GCase) stops working properly. When GluSph levels rise, it creates a toxic environment inside brain cells, triggering the buildup of harmful proteins, draining cells of energy and disrupting the routine cleanup processes neurons rely on to stay healthy.
In participants who entered the study with high GluSph levels, treatment with GT-02287 led to an average 81% reduction in GluSph in cerebrospinal fluid after 90 days. Importantly, this is the first time such a reduction has been observed in people with Parkinson’s disease receiving a GCase-modulating therapy, suggesting that the drug is reaching the brain and restoring enzyme activity where damage accumulates.
Rather than masking downstream effects of disease, the data indicate GT-02287 may be acting closer to Parkinson’s biological roots.
Biomarkers alone do not tell the whole story, and Gain Therapeutics has been careful not to overstate the clinical implications. The Phase 1b study was designed primarily to assess safety and biological engagement, not efficacy. Still, early functional signals are beginning to emerge.
Of the 19 participants who completed the initial 90-day dosing period, 15 were included in the analysis of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). On average, these participants showed a 2.2-point improvement across daily living and motor function scores. While modest, stabilization or improvement over such a short period stands out in a condition typically defined by gradual decline.
Gene Mack, President and CEO of Gain Therapeutics, framed the findings as a meaningful convergence of biology and patient experience.
“These results mark an important step forward for our program,” he said. “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 [1].”
Lead investigator Michele DeSciscio emphasized the need for patience, but acknowledged the early promise.
“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,” she said, pointing to the importance of longer-term follow-up.
This update builds on data released in December 2025, when Gain Therapeutics first reported reductions in GluSph as a prespecified exploratory endpoint of the Phase 1b study [2]. At that time, all participants with elevated baseline GluSph showed large decreases toward levels seen in healthy individuals, an early sign of central nervous system target engagement rarely demonstrated in Parkinson’s trials.
“We are excited by the unfolding biomarker evidence of GT-02287 activity and central nervous system target engagement,” Mack said in December. He added that reducing GluSph in the brain could directly support neuronal health and translate into observable clinical benefits over time.
Taken together, the December and current results suggest consistency, an important distinction in early-stage neurodegenerative research.
The longevity sector views GT-02287 as a representation more than a Parkinson’s drug. Lysosomal dysfunction, protein misfolding and mitochondrial stress are hallmarks not only of Parkinson’s but of aging itself. By restoring protein function through allosteric modulation, Gain Therapeutics is targeting a shared vulnerability across multiple age-related diseases.
This approach aligns with a broader shift in longevity biotech: moving upstream to preserve cellular resilience before irreversible damage sets in. It also helps explain why GT-02287 is being explored beyond Parkinson’s, with potential relevance to conditions such as dementia with Lewy bodies and Alzheimer’s disease.
Participants in the Phase 1b study can now continue treatment for up to 12 months, with extended data expected in 2026.
Gain Therapeutics plans to present longer-term findings at the AD/PD conference in March, offering insight into durability, progression and whether early biomarker changes translate into sustained functional benefit.
[1] https://gaintherapeutics.com/newsroom/press-releases/press-releases-2026/gain-therapeutics-highlights-biomarker-evidence-supporting-disease-modifying-potential-of-gt-02287/
[2] https://gaintherapeutics.com/newsroom/press-releases/press-releases-2025/gain-therapeutics-announces-positive-results-in-key-exploratory-endpoint-from-its-phase-1b-clinical-study-of-gt-02287-in-people-with-parkinsons-disease/
