Allosteric therapy targets common genetic cause of Parkinson’s

Parkinson's disease

Gain Therapeutics has initiated a Phase I clinical trial of GT-02287, the company’s lead drug candidate for the treatment of GBA1 Parkinson’s disease.

Preclinical data demonstrated that GT-02287 can restore the function of the lysosomal enzyme glucocerebrosidase (GCase), which becomes misfolded and dysfunctional due to a GBA1 gene mutation, the most common genetic risk factor for the development of Parkinson’s disease.

Restoring GCase function with GT-02287 was shown to have a profound effect in animal models of Parkinson’s disease on the entire disease cascade, including a neuroprotective effect on dopaminergic neurons and improvement of motor deficiencies. Based on these data, GT-02287 has the potential to slow or even stop the progression of Parkinson’s disease.

“Initiating first-in-human dosing with GT-02287 is an important milestone for Gain as we enter a new era as a clinical-stage company,” said Matthias Alder, Chief Executive Officer of Gain Therapeutics. “I am very proud of the work accomplished by the entire Gain team to get us to this stage today, and we are eager to advance our understanding of the safety, tolerability and effect of GT-02287 in humans.”

Potential in other neurodegenerative diseases

The Phase I trial is a single centre, randomised, double-blind, placebo-controlled, single- and multiple-ascending dose (SAD/MAD) study to evaluate the safety and tolerability of GT-02287 administered orally once daily in healthy adults.

The secondary objective is to evaluate the pharmacokinetics of SAD and MAD dose levels to identify a maximum tolerated dose (MTD) and identify recommended doses for further clinical development. As an additional exploratory endpoint, this study will look at GCase target engagement and activity in blood for an early clinical validation of the effect of GT-02287 on GCase.

“Today marks an important step for Gain in the journey to bring a novel, potentially disease-modifying therapy to patients for whom only symptom-focused therapeutics exist,” said Dr Robin Ely, Director, Integrative and Regenerative Medicine; Founder, National Gaucher Foundation; and Clinical-Scientific Consultant to NGF Global Diagnostic and Treatment Initiative. “If GT-02287 proves successful in disrupting the disease process in GBA1 Parkinson’s, its fundamental mechanism of action could play a crucial role in addressing various neurodegenerative diseases, including Gaucher, idiopathic Parkinson’s, dementia with Lewy bodies, and Alzheimer’s disease.”

Gain’s pipeline of novel allosteric therapies, including GT-02287, was discovered via the company’s SEE-Tx drug discovery platform, which uses AI-supported 3D structural biology and supercomputer-powered proprietary physics-based models.

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