Treatment with GT-02287 Resulted in a Significant Dose-Dependent Improvement of Cellular Lysosomal Health and Fine Motor Skills
Results Presented at the International Congress of Parkinson’s Disease and Movement Disorders 2022 Annual Meeting in Madrid, Spain
Gain Therapeutics, Inc. (Nasdaq: GANX) (“Gain”, or the “Company”), a biotechnology company transforming drug discovery with its proprietary computational drug discovery platform identifying novel allosteric binding sites and creating small molecule treatments, today announced the presentation of new preclinical data at the International Congress of Parkinson’s Disease and Movement Disorders 2022 Annual Meeting in Madrid, Spain, evaluating the neuroprotective effect of Gain’s lead ‘Structurally Targeted Allosteric Regulator’ (STAR) compound, GT-02287, in preclinical in vitro and in vivo models of Parkinson’s disease.
The results from these latest in vitro and in vivo studies are consistent with previous data presented by the Company and demonstrate statistically significant, dose-dependent effects of GT-02287, the Company’s lead compound for the treatment of Parkinson’s disease. First, by protecting against key pathophysiological hallmarks of Parkinson’s disease, including neurite and lysosomal pathology, and second, by reducing fine motor skill impairment in mice (Wire Hang Test) in conduritol β-epoxide (CBE) models designed to mimic the neurodegenerative effects of Parkinson’s disease.
“We are especially excited by these latest data which expand on the accumulating preclinical evidence supporting the potential disease-modifying properties of our novel small molecule candidate, GT-02287,” said Joanne Taylor, Ph.D., Senior Vice President of Research at Gain Therapeutics. “Collectively, the body of preclinical data that has been generated is highly encouraging as it shows that GT-02287 may be able to intervene early in the disease process by restoring proper enzyme function and lysosomal health, thereby improving cell survival with the goal of ultimately halting disease progression. If these results are supported in future clinical studies, GT-02287 could become an important first-in-class disease-modifying therapy for Parkinson’s disease.”
Summary of the Preclinical Data
In a poster presentation on September 17, 2022, entitled “GT-02287, A Brain-penetrant Structurally Targeted Allosteric Regulator of Glucocerebrosidase Shows Evidence of Pharmacological Efficacy in Conduritol β-epoxide (CBE) Models of Parkinson’s Disease,” Gain scientists showcased new preclinical data evaluating the neuroprotective effects of GT-02287 following CBE administration.
In the first study, the ability of GT-02287 to neutralize CBE-mediated neurodegeneration was evaluated in rat mesencephalic neurons. In this study, CBE (100 µM) was applied followed by administration of GT-02287 at either 4 or 24 hours post CBE insult at doses of 1 µM or 12.5 µM. Three days following insult with CBE, neuronal cultures were fixed and stained for tyrosine hydroxylase (TH), a marker for dopaminergic neurons. Neuronal survival, neurite network and lysosomal health (LAMP-2 staining) parameters were all evaluated. The results showed that GT-02287 produced a statistically significant therapeutic effect on both the mesencephalic neurite network and overall lysosomal health, supporting results from earlier preclinical studies showing that enhancement of lysosomal glucocerebrosidase (GCase) activity by GT-02287 protects against the key pathophysiological hallmarks of Parkinson’s disease.
In a follow-up behavioral assessment study evaluating the neuroprotective effects of GT-02877 in a mouse CBE/α-synuclein model, mice were bilaterally injected with α-synuclein preformed fibril (PFF) into the striatum and administrated daily for fifteen days with the CBE (intraperitoneally) and GT-02287 treatment (orally, once per day) at doses of 30 mg/kg, 60 mg/kg or 90 mg/kg for fourteen days. Fine motor skills were then assessed (ability to grasp and hang onto a wire) and compared to results from vehicle control and untreated animals. At each dose level and in a dose-dependent manner, GT-02287 demonstrated statistically significant improvements in locomotor deficits compared to CBE/α-synuclein-injured animals, confirming the neuroprotective benefit observed in vitro in this industry standard Parkinson’s disease in vivo locomotor model.
Through its proprietary SEE-Tx® platform, Gain has identified GT-02287, the Company’s lead compound for Parkinson’s disease, which has the ability to restore the function of GCase, the misfunction of which is implicated in various neurodegenerative diseases. The compound has been characterized in numerous assays and showed the potential to halt disease progression in Parkinson’s patients with GBA1 gene mutations as well as patients whose glucocerebrosidase (GCase) protein was misfolded due to ageing cellular processes. This work was supported through grants from The Michael J. Fox Foundation (MJFF) and the Silverstein Foundation for Parkinson’s with GBA and certain of its findings have been presented by Gain scientists and collaborators at previous medical conferences.
The poster presented from the MDS Congress in Madrid is available on the Science & Technology section of the Company’s website at https://www.gaintherapeutics.com/science-technology/posters.html.
About Parkinson’s Disease
Mutations
in the GBA1 gene, encoding the lysosomal enzyme GCase, represents the
most common genetic risk factor for Parkinson’s disease (PD). Impaired
GCase function has garnered attention due to its association with
α-synuclein pathology in GBA-associated PD patients, and also in
sporadic PD, as well as in related α-synucleopathies. Although less
investigated, decreased GCase levels and activity are also implicated in
the pathophysiology of Alzheimer’s disease (AD). Enhancing the activity
of mutant and wild-type GCase may represent a therapeutic strategy for
the treatment of a range of neurodegenerative diseases.
Gain Therapeutics, Inc. is transforming drug discovery with its proprietary computational discovery platform identifying novel allosteric binding sites and creating small molecule treatments to address unmet medical needs. The ability to identify never-seen-before allosteric targets on proteins involved in diseases across the full spectrum of therapeutic areas provides opportunities for a range of drug-protein interactions, including protein stabilization, protein destabilization, targeted protein degradation, allosteric inhibition, and allosteric activation. Gain’s pipeline spans neurodegenerative diseases, lysosomal storage disorders, and oncology. Gain’s lead program in Parkinson’s disease has been awarded funding support from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and The Silverstein Foundation for Parkinson’s with GBA, as well as from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and Innosuisse.
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