Topline results from a study that tested two lead structurally targeted allosteric regulator (STAR) compounds ― GT-02287 and GT-02329 ― are promising for the treatment of Gaucher disease (GD) and GBA1-associated Parkinson's disease (PD).
"The topline data demonstrates that our STARs compounds open a new potential approach for direct treatment of GBA1 Parkinson's disease by guiding misfolded forms of the GCase enzyme to their proper shape and restoring enzymatic activity," Manolo Bellotto, PhD, general manager at Gain Therapeutics, said in a news release.
"This is an exciting validation of our platform technology and a promising potential therapeutic opportunity for patients suffering from these debilitating diseases," Bellotto said.
The GBA1 gene encodes glucocerebrosidase (GCase), a lysosomal enzyme. Mutations in the GBA1 gene are among the most commonly known genetic risk factors for the development of PD and related synucleinopathies.
GBA1 mutations also cause GD, a rare autosomal storage disorder. Mutations may lead to the degradation of the protein, as well as disruptions in lysosomal targeting and diminished performance of the enzyme in the lysosome.
Patients with GD are at increased risk of developing PD and dementia with Lewy bodies.
"Our laboratory is using human induced pluripotent stem cells (iPSC) derived from patients with GD and GBA-associated Parkinson's disease to test the efficacy of the two lead STAR chaperones developed by Gain Therapeutics," lead investigator Ricardo Feldman, PhD, with the University of Maryland School of Medicine, Baltimore, Maryland, said in the news release.
The studies using iPSC-derived cortical and dopaminergic neurons from patients with neuronopathic GD demonstrate that these compounds increase the levels of GCase protein, its transport to the lysosome, and its enzymatic activity, Feldman noted.
In dopaminergic neurons, the two compounds also decrease the levels of α-synuclein-p129, "demonstrating their potential to treat GBA1-associated Parkinson's disease," he added.
"These data are extremely exciting, as it further demonstrates the potential of GT-02287 and GT-02329 and expands the body of evidence supporting our site-directed enzyme enhancement therapy (SEE-Tx) drug discovery platform," said Gain CEO Eric Richman.
"These encouraging results show promise for this approach to correct dysfunction in the GBA1 pathway, a leading target for Parkinson's drug development," Marco Baptista, PhD, vice president of research programs for the Michael J. Fox Foundation, said in the release.
"We look forward to hearing more on next steps to advance these potential therapies further in testing and closer to patients whose greatest unmet need is a treatment to slow or stop disease progression," Baptista said.
Gain Therapeutics plans to present complete results from the study of GT-02287 and GT-02329 at the upcoming Michael J. Fox Foundation Innovating From Drug Discovery to the Clinic: Novel Approaches to PD Therapeutic Development webinar.
The company also anticipates launching studies of the two compounds that will support an investigational new drug application for GD and PD later this year.
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Cite this: Positive Topline Results for Novel Parkinson's Treatment - Medscape - Sep 08, 2021.