Gain Therapeutics’ candidate compound for Parkinson’s Disease demonstrated the ability to increase GCase protein levels and enhance neuronal activity.
Gain Therapeutics is generating some excitement in the neurodegenerative research field. Its candidate compound for Parkinson’s Disease demonstrated the ability to increase GCase protein levels and enhance neuronal activity, according to preclinical data shared at the 2022 Synuclein Meeting in Belgium.
In its poster presentation, Gain’s initial data showed that lead compound GT-02287 was able to increase activity levels of beta-glucocerebrosidase proteins, improve lysosomal health, correct abnormal PD phenotypes, including alpha-synuclein, and enhance neuronal connections and neuron survival. GT-02287 is orally bioavailable and can penetrate the brain.
The data used for the presentation, titled “Targeting Glucocerebrosidase with Structurally Targeted Allosteric Regulators Corrects Abnormal Phenotypes in Models of Parkinson’s Disease,” was taken from two in vitro models: a BE2-M17 dopaminergic neuron linked to Parkinson’s pathology and a CBE model of rat neurons.
“Our lead candidate, identified with the proprietary SEE-Tx drug discovery platform, can allosterically bind and stabilize GCase, thus avoiding its degradation and allowing its transport to the lysosomes where the enzyme can carry out its biological function. The new data builds on a body of evidence showing a beneficial effect of our lead candidate on enzyme levels, substrate depletion, lysosomal health, and most importantly for disease pathology, neuronal health,” commented Manolo Bellotto, the president and general manager of Gain Therapeutics, in a statement.
Parkinson’s Disease, which affects over six million people worldwide, is associated with GBA1 gene mutations, which affect the GCase enzyme’s ability to function, leading to the known PD symptoms. Enhancing the activity of mutant and wild-type GCase, which GT-02287 appears to be capable of doing, offers a potential treatment strategy for Parkinson’s and other neurodegenerative disorders.
Gain first shared preclinical data of GT-02287 in November 2021 during a poster session at the Society for Neuroscience Annual Meeting. At the time, researchers presented data on its ability to improve behavioral deficits linked to PD and reduce synuclein pathology and information. It also demonstrated a favorable toxicity profile.
Gain now has two candidates in preclinical trial stages, with the Parkinson’s Disease candidate joining the one it is developing for Gaucher Disease, a lysosomal storage disorder caused by GBA mutations that still has no cure. The majority of Gain’s programs are still in the research and discovery phases, including candidates for gangliosidosis, Krabbe disease, metachromatic leukodystrophy and mucopolysaccharidosis type 1.
“The data we presented at the Synuclein Meeting demonstrates further encouraging disease modifying potential for patients with Parkinson’s disease who currently have no effective treatment options,” added Eric Richman, Gain’s chief executive officer.
Research and development efforts for GT-02287 are done with the help of partners such as The Michael J. Fox Foundation, the Silverstein Foundation, the University of Maryland School of Medicine and Innosuisse: Eurostars.
Shares in Gain Therapeutics instantly surged to $6 per share shortly on April 12 after the company announced the good news on GT-02287, but later calmed down to close at $3.88 per share.
