Gain Therapeutics Presents New Preclinical Data of Drug Candidate for Parkinson’s Disease
Gain Therapeutics have announced preclinical data demonstrating the Company’s lead drug candidate GT-02287 significantly decreased Parkinson’s disease (PD)-associated pathology and improved motor dysfunction in two different preclinical models of Parkinson’s disease. Of note, GT-02287 significantly reduced plasma Neurofilament Light Chain (NfL) levels, an emerging biomarker for neurodegeneration, in a mouse model of GBA1-PD. The findings are being presented in two posters, including one that was accepted as a late breaking abstract, at the International Congress of Parkinson's Disease and Movement Disorders being held in Copenhagen, Denmark from August 27-31, 2023.
“The compelling data from two preclinical Parkinson’s disease models with our lead drug candidate GT-02287 show that this orally administered allosteric regulator of GCase restored enzymatic function and significantly reduced the pathological hallmarks and motor dysfunction associated with Parkinson’s disease,” said Joanne Taylor, Ph.D., Senior Vice President of Research at Gain. “GT-02287 also markedly decreased plasma NfL, an emerging and important neurodegeneration biomarker that can be measured in blood, which is very exciting as we consider its application in clinical trials.”
The first poster titled “Neuroprotective effect of GT-02287, a brain-penetrant structurally targeted allosteric regulator of glucocerebrosidase, leads to a significant reduction of plasma NfL levels and improvement in behavioural deficits in a mouse model of GBA1 Parkinson’s disease” (Late-breaker Abstract #LBA-13) will be presented by Dr. Taylor on each poster presentation date between 13:00 and 15:00 in the exhibition hall.
Researchers used a mouse model of GBA1-PD, created using conduritol beta epoxide (CBE) to induce GCase deficit comparable to GBA1-PD. Oral administration of GT-02287 over 14 days significantly reduced aggregated α-synuclein, neuroinflammation and neuronal death in the brain. Treatment with GT-02287 also increased tyrosine hydroxylase (TH) immunostaining, a marker of dopaminergic neurons, as well as dopamine levels, and improved motor strength and motor coordination.
Prominently, GT-02287 significantly reduced plasma NfL levels in this GBA1-PD model. The emerging neurodegeneration biomarker was previously accepted by the U.S. Food and Drug Administration (“FDA”) for the accelerated approval of tofersen for the treatment of amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS) and was recommended by the FDA as an exploratory endpoint for neuronopathic mucopolysaccharidosis II (MPS II) clinical trials.
Dr. Taylor will also present a second poster on August 30th between 13:00 and 15:00 titled “GT-02287, a brain-penetrant structurally targeted allosteric regulator for glucocerebrosidase shows evidence of pharmacological efficacy in an animal model of Parkinson’s disease”(Abstract #1376). Data from the poster describes the effect of GT-02287 on rotenone-induced neurotoxic effects in a PD animal model. GT-02287 restored GCase levels in the brain and reduced the accumulation of toxic GCase substrates in the cerebrospinal fluid. Additionally, GT-02287 reduced aggregated α-synuclein and TNF-α levels, improved lysosomal health, as well as increased TH expression levels in the substantia nigra.