Oral GT-02287 seen to safety reach adult brain cells in Phase 1 trial
Therapy aims to raise activity of enzyme working against toxic alpha-synuclein
An investigational treatment for Parkinson’s disease known as GT-02287 safely led to a roughly 53% increase in GCase enzyme activity, as measured in dried blood spots from treated healthy adults relative to those given a placebo in a Phase 1 clinical trial, its developer, Gain Therapeutics, reported.
This enzyme is an important component of a cell part called the lysosome, where enzymes work as cellular garbage disposal units, breaking down materials from outside the cell as well as their own excess or worn-out components. The GBA gene provides instructions for producing the GCase, or beta-glucocerebrosidase, enzyme. GBA mutations are one of the most common genetic causes of Parkinson’s, and associated with early-onset disease.Â
The company plans to initiate a Phase 1b trial of GT-02287 in Parkinson’s patients before the close of December, further assessing the potential therapy’s safety and tolerability, as well as its proof-of-concept as a potentially effective treatment. GT-02287, Gain reports in a company investor release, is intended to treat patients with and without GBA mutations, as it may slow disease progression.
GT-02287 is designed to restore GCase activity, preventing toxic buildup in cells
Gain also announced plans to meet with U.S. Food and Drug Administration officials to discuss ways to optimize GT-02287’s development and improve its chances of its being approved.
When the GCase enzyme is missing or not functioning properly, the lysosome cannot break down toxic substances like the abnormal alpha-synuclein protein. Clumps of toxic alpha-synuclein, known as Lewy bodies, that spread through brain cells are a disease hallmark, and thought to drive progression.
GT-02287, an oral small molecule, is designed to bind to the GCase enzyme and restore its function, lowering alpha-synuclein clumping and protecting nerve cells from degeneration, the disease’s cause.
Studies in a mouse model of Parkinson’s associated with GBA mutations found that a once-daily treatment with GT-02287 improved motor and cognitive skills in the animals. Additional mouse studies determined that the treatment could improve nerve cell health and protect dopamine-producing neurons, a critical group of nerve cells affected by Parkinson’s.
GT-02287 also was seen to slow or stop the disease progression in Parkinson’s mouse models without GBAÂ mutations.
Clinical trial in Parkinson’s patients to test 3 months of GT-02287 treatment
The Phase 1 clinical trial assessed GT-02287’s safety and pharmacokinetics — its movement into, through, and out of the body — at varying doses in 72 healthy adults up to age 64 in Australia.
Treatment was found to be safe and well tolerated, and it could be measured in the cerebrospinal fluid that surrounds the brain and spinal cord, indicating GT-02287 could enter its target area, the brain. Fluid levels of GT-02287 measured in trial participants were consistent with those observed in rodents given a therapeutically effective dose of the drug, Gain reported.
Trial researchers also examined GCase activity in blood spots from treated and placebo study groups, and found it to be about 53% higher in adults given GT-02287, indicating the therapy engaged with the targeted enzyme, enhancing its activity.
The Phase 1b trial in Parkinson’s patients, expected to begin soon, will test the safety and tolerability of three months of treatment and be open label, meaning GT-0228 will be given to all those enrolled, the company announced.
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