Mouse models of GBA1 Parkinson’s disease that are treated with Gain Therapeutics’ clinical-stage drug appear to have better cognitive function and lower disease biomarkers than untreated animals.
The biotech unveiled new preclinical data for the candidate, dubbed GT-02287, at the Federation of European Neuroscience Societies (FENS) Forum June 27.
“These data further confirm our conviction that GT-02287 can slow or stop progression of Parkinson’s disease and given the cognitive decline observed in GBA1 Parkinson’s patients, we hope that we can one day deliver this drug to those that need it and help them improve their everyday life,” Joanne Taylor, Ph.D., senior vice president of research at Gain, said in a press release.
To perform the study presented at FENS, the researchers used daily doses of toxins to induce the murine equivalent of GBA1 Parkinson’s disease. Eight days after they initiated the toxins, they began injecting a group of them once a day with GT-02287. They continued to administer both the toxin and the Parkinson’s drug for 20 more days in that group, while an untreated control group received only the toxins.
To see whether the drug worked, Gain scientists investigated the animals’ ability to build nests—a complex behavior that requires a high degree of mental function—along with their motor skills, which Gain looked at in an earlier study, too. They found the mice with Parkinson’s that were given GT-02287 built nests that looked similar to those of healthy animals, while the nests of mice that didn’t receive treatment were poorly constructed.
The differences lined up with relative levels of neurodegeneration biomarkers, too: Treated mice had lower amounts of the proteins neurofilament light chain, alpha-synuclein, GFAP and Iba-1 in their brains.
“These data further support the potential of GT-02287 as a disease-modifying therapy for the treatment of [GBA1 Parkinson’s disease] that is already clinically established, including improvement in activities of daily living and cognition,” Gain’s poster read.
GT-02287 restores the function of an enzyme called glucocerebrosidase, or GCase, which is found in the lysosomes of neurons. Under normal conditions, the enzyme breaks down a lipid called glucosylceramide. But certain mutations in GCase’s encoding gene, GBA1, prevent it from functioning properly. That ultimately results in the buildup of alpha-synuclein and other inflammatory molecules, leading to Parkinson’s disease. GBA1 mutations are the most common gene variants associated with the condition.
So far, GT-02287 appears to be safe in healthy people, as data from an early phase 1 study showed in April. Gain anticipates starting a three-month phase 1b trial in 20 to 30 GBA1 Parkinson's disease patients in the second half of 2024, with a readout in the first half of 2025, according to a corporate presentation given in June.