Gain Therapeutics Unveils Preclinical GT-02287 Data at Neuroscience 2024

Gain Therapeutics, Inc., a biotechnology company focused on advancing allosteric small molecule therapies, recently presented new findings on GT-02287 at the Society for Neuroscience (SfN) 2024 conference held in Chicago. GT-02287, the company's lead drug candidate, shows promise as a disease-modifying therapy for both GBA-1 and idiopathic Parkinson’s disease.

In preclinical animal models, GT-02287 demonstrated sustained improvement in motor and cognitive functions even after treatment cessation. This effect persisted for more than a week, indicating a potential long-term benefit of the drug in treating Parkinson’s disease. Furthermore, another presentation highlighted GT-02287's role in enhancing mitochondrial function and providing neuroprotection in GBA1-Parkinson’s disease models.

A significant discovery was also made regarding the drug’s ability to prevent Tau accumulation in cell models. This finding suggests that GT-02287 might be effective in treating tauopathies such as Alzheimer’s disease. Tau accumulation was notably reduced in both GBA-1 mutation and wild-type cell lines treated with GT-02287.

Joanne Taylor, Ph.D., Senior Vice President of Research at Gain Therapeutics, stated that the preclinical data reinforces the potential of GT-02287 as a disease-modifying therapy for Parkinson’s patients. The drug was observed to rescue motor deficits and prevent cognitive decline, effects that persisted post-treatment. Additionally, GT-02287 showed benefits in mitochondrial and lysosomal health, addressing the cascade of disease processes resulting from glucocerebrosidase (GCase) enzyme dysfunction.

Interim CEO and CFO Gene Mack emphasized the preservation of motor and cognitive improvements in Parkinson’s disease models, even after discontinuation of GT-02287. This highlights the drug’s potential to halt or slow Parkinson’s disease progression. The therapeutic target, GCase, appears promising beyond Parkinson’s disease, offering potential for broader applications.

In the late-breaking poster titled, “GT-02287, a clinical stage GCase regulator, demonstrates disease modifying capacity in both GBA1 and idiopathic Parkinson’s disease models,” researchers presented findings from animal models. GT-02287 was administered after establishing a clinical phenotype and then withdrawn from half the subjects for over a week. Performance in neuromuscular, motor coordination, and daily living activities was measured through various tests. GT-02287 rescued deficits in these functions and its discontinuation did not significantly affect performance, indicating its disease-modifying effect.

Another poster, “GT-02287, a clinical stage GCase regulator, improves mitochondrial function and provides a neuroprotective effect in GBA1-Parkinson's disease models,” detailed in vitro and in vivo models. In vitro tests with rat neurons treated with CBE to mimic GCase activity reduction showed that GT-02287 reduced mitochondrial reactive oxygen species, ameliorated lysosomal pathology, reduced α-synuclein aggregation, and provided neuroprotection. In vivo tests with mice subjected to CBE and α-synuclein PFFs injected into the striatum showed that delayed administration of GT-02287 reduced mitochondrial protein Miro1, aggregated α-synuclein, and plasma neurofilament light chain (NfL), fully restoring motor function.

The final poster, “GT-02287, a GCase modulator and Gain Therapeutics’ PD drug candidate prevents Tau accumulation in a cellular model,” detailed GT-02287’s effect on Tau accumulation in human fibroblasts with either the L444P mutant or wild-type GBA. GT-02287 reduced Tau accumulation in both cell types, demonstrating its potential for treating Alzheimer’s disease and other tauopathies.

GT-02287’s preclinical successes mark a significant milestone in developing treatments for Parkinson’s disease and potentially other neurodegenerative diseases. Gain Therapeutics continues to explore GT-02287's capabilities, leveraging support from notable organizations such as The Michael J. Fox Foundation and The Silverstein Foundation for Parkinson’s with GBA.