Gain's GDP1 Parkinson's drug aids cognitive retention in mice

Gain Therapeutics has presented encouraging new preclinical data for its clinical-stage drug candidate, GT-02287, which is aimed at treating GBA1 Parkinson’s disease. The findings were unveiled at the Federation of European Neuroscience Societies (FENS) Forum on June 27.

GT-02287 has shown promise in improving cognitive function and reducing disease biomarkers in mouse models of GBA1 Parkinson’s disease. Joanne Taylor, Ph.D., Senior Vice President of Research at Gain, expressed hope that the drug could eventually slow or halt the progression of Parkinson’s disease, particularly addressing the cognitive decline seen in GBA1 Parkinson’s patients.

The study, showcased at FENS, involved using toxins to induce a murine model of GBA1 Parkinson’s disease. Researchers began administering the drug GT-02287 to a group of these mice daily, eight days after toxin exposure. This treatment continued for 20 days, while a control group received only the toxins and no treatment.

One key aspect of the study was evaluating the animals' ability to build nests, a complex behavior indicative of high mental function. Researchers also assessed motor skills, as examined in a previous study. The results were promising: mice treated with GT-02287 built nests that resembled those of healthy mice, whereas untreated mice constructed poorly formed nests.

This improvement in nest-building behavior correlated with lower levels of neurodegeneration biomarkers in the treated mice. Specifically, treated animals showed reduced levels of neurofilament light chain, alpha-synuclein, GFAP, and Iba-1 proteins in their brains.

The study's findings support the potential of GT-02287 as a disease-modifying therapy for GBA1 Parkinson’s disease. Gain's research poster highlighted that the drug could enhance activities of daily living and cognition in patients.

The mechanism of action for GT-02287 involves restoring the function of an enzyme called glucocerebrosidase (GCase), located in the lysosomes of neurons. Under normal conditions, GCase breaks down a lipid known as glucosylceramide. However, mutations in the GBA1 gene, which encodes GCase, can impair its function, leading to the accumulation of alpha-synuclein and other inflammatory molecules, ultimately causing Parkinson’s disease. GBA1 mutations are the most common genetic variants linked to Parkinson’s disease.

So far, GT-02287 has demonstrated safety in healthy individuals, as shown in data from an early phase 1 study released in April. Gain Therapeutics plans to initiate a three-month phase 1b trial involving 20 to 30 patients with GBA1 Parkinson’s disease in the latter half of 2024, with results expected in the first half of 2025.