Insights on GBA1-Targeting Agent GT-02287 for Parkinson Disease: Joanne Taylor, PhD

WATCH TIME: 7 minutes

"Our preclinical findings show that GT-02287 not only targets the root causes of Parkinson disease but also holds promise for other neurodegenerative diseases with similar protein aggregate and mitochondrial dysfunction involvement."

GT-02287 (Gain Therapeutics), an orally administered, brain-penetrant small molecule, is designed to restore the function of the lysosomal enzyme glucocerebrosidase (GCase) in patients with GBA1 Parkinson disease (PD). According to the company, the agent was discovered via Gain’s Site-directed Enzyme Enhancement Therapy (SEE-Tx) drug discovery program.¹ In preclinical models, investigators observed that the agent restored GCase enzymatic function, reduced aggregated α-synuclein, neuroinflammation and neuronal death, increased dopamine levels, and improved motor function.

In October 2023, the company announced that dosing commenced for the phase 1 trial of GT-02287 in healthy individuals.¹ The trial is a randomized, double-blind study that features both a single- (SAD) and multiple-ascending dose (MAD) component. Mainly intended to evaluate the safety and tolerability of GT-02287, the study includes several secondary objectives such as the pharmacokinetics of SAD and MAD dose levels to identify a maximum tolerated dose as well as identify recommended doses for further clinical development. The trial will also assess the agent’s impact on GCase, which becomes misfolded and dysfunctional because of the GBA1 gene mutation.

Recently, Joanne Taylor, PhD, senior vice president of research at Gain Therapeutics, sat down in an interview with NeurologyLive® to share some of her scientific insights on the agent such as its mechanism of action and implications from preclinical data. She talked about how GT-02287 aims to address the cellular dysfunctions associated with PD by targeting the GCase. Beyond Parkinson, she spoke about the evidence that suggests GT-02287, might have applications in other neurodegenerative diseases such as Alzheimer disease. With GT-02287 in a phase 1 clinical trial, Taylor discussed some of the biomarkers that are being examined to assess its neuroprotective effects in healthy patients.

REFERENCES
1. Gain Theraprutics announces dosing of first two subjects in phase 1 clinical trial of GT-02287, a novel CGase-targeting small molecule therapy for GBA1 Parkinson’s disease. News release. Gain Therapeutics. October 4, 2023. Accessed January 26, 2024. https://www.globenewswire.com/news-release/2023/10/04/2754433/0/en/Gain-Therapeutics-Announces-Dosing-of-First-Two-Subjects-in-Phase-1-Clinical-Trial-of-GT-02287-a-Novel-GCase-targeting-Small-Molecule-Therapy-for-GBA1-Parkinson-s-Disease.html