Parkinson’s therapy safely increases GCase activity in healthy volunteers
Gain's GT-02287 shows promising efficacy results in Phase 1 trial
GT-02287, a potential therapy for Parkinson’s disease, showed promising results in a Phase 1 clinical trial involving healthy volunteers, according to data announced by developer Gain Therapeutics.
The investigational treatment was found to be safe and well tolerated at doses projected to be effective in people with the neurodegenerative disease. GT-02287 also increased, by up to 30%, the activity of the GCase enzyme that is typically reduced in Parkinson’s patients with GBA1 gene mutations.
Gain said it expects the therapy’s effect to be even more pronounced in Parkinson’s patients, who likely lack the proper mechanisms to fine-tune GCase activity. These results support the company’s plans to advance GT-02287 into a clinical trial involving patients with and without GBA1 mutations by year’s end.
“We remain enthusiastic about the promising profile of GT-02287 and look forward to initiating a trial … with the goal of demonstrating safety and tolerability in patients … and obtaining proof of mechanism based on relevant biomarkers,” Gene Mack, Gain’s interim CEO and chief financial officer, said in a company press release.
The trial results were presented at the International Congress of Parkinson’s Disease and Movement Disorders, held Sept. 27 through Oct. 1 in Philadelphia. The poster was titled “The novel glucocerebrosidase chaperone GT-02287 in development for GBA-PD is safe and well tolerated in healthy volunteers at oral doses that produce plasma exposures in the projected therapeutic range.”
Parkinson’s therapy candidate increased GCase activity up to 30%
For Jonas Hannestad, MD, PhD, Gain’s chief medical officer, the clinical data “[confirm] our conviction that GT-02287 may be able to slow or stop the progression” of Parkinson’s disease.
“We hope that one day we can deliver this drug to those that need it and help them improve their everyday quality of life,” Hannestad said.
Mutations in the GBA1 gene are the most common genetic risk factor for Parkinson’s disease. The gene codes for glucocerebrosidase, known for short as GCase, an enzyme that breaks down fatty molecules for recycling within cells. When mutated, the enzyme loses activity and causes the accumulation of toxic deposits, including those formed by misfolded proteins like alpha-synuclein.
GT-02287 is an oral small molecule designed to bind to the GCase enzyme and restore its activity. This is expected to prevent alpha-synuclein from clumping in the brain, slowing the progression of Parkinson’s symptoms.
The Phase 1 clinical trial tested the safety and tolerability of the Parkinson’s therapy candidate relative to a placebo in 73 healthy volunteers, comprising 40 men and 33 women. The study also tested GT-02287’s pharmacokinetics — how it moves into, through, and out of the body — when given as single or multiple ascending doses once daily for up to 14 days.
GT-02287 was generally safe and well tolerated, with mostly mild, short-lasting side effects. The most common side effects were nausea and headache, and no serious side effects were reported. One participant experienced a transient, mild elevation of liver enzymes, a sign of liver damage, after a single dose of GT-02287.
These results support continued development of GT-02287 as a potential disease-slowing treatment for [Parkinson’s disease].
At daily doses of 7.7 mg/kg and higher, GT-02287 reached blood levels within the projected therapeutic range and was measurable in the cerebrospinal fluid, the liquid that surrounds the brain and spinal cord, showing its ability to reach the brain.
Unlike a placebo, GT-02287 increased GCase activity by about 30% in the blood of healthy volunteers, showing target engagement — that is, binding of the small molecule to the GCase enzyme, whose activity continued to rise 12 hours after dosing, even after 14 days, the last time point analyzed.
“These results support continued development of GT-02287 as a potential disease-slowing treatment for [Parkinson’s disease],” the researchers wrote.
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