$5 million Fox Foundation grant targets GBA1 Parkinson’s research
Congruence Therapeutics eyes development of molecules tied to gene mutations
The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has awarded a $5 million grant to Congruence Therapeutics to advance the development of small molecules for Parkinson’s disease associated with mutations in the GBA1 gene.
The research grant will support the optimization and clinical development of therapeutic candidates that can enter the brain and enhance the activity of the glucocerebrosidase (GCase) enzyme, which is produced by the GBA1 gene. Mutations in GBA1 are the most significant known genetic risk factor for Parkinson’s disease.
The project, “Allosteric Small Molecule Therapies for Treating GBA1-PD,” was presented by the company at the GBA1 Meeting 2025, held in June in Montreal.
“We are honored to receive this grant from The Michael J. Fox Foundation. Their confidence strengthens our commitment to apply Congruence’s computational drug discovery tools toward the development of GCase-targeting therapies that bring hope to the Parkinson’s community,” Clarissa Desjardins, PhD, CEO of Congruence, said in a company press release.
Computational drug discovery engine will study GBA1 mutations
Parkinson’s is caused by the dysfunction and loss of nerve cells involved in motor control, called dopaminergic neurons. In some patients, the disease is triggered by mutations in the GBA1 gene, which are associated with earlier disease onset, faster disease progression, and more rapid cognitive decline.
Such mutations result in the formation of a dysfunctional version of the GCase enzyme that’s important for the function of lysosomes, the cellular compartments that recycle cellular waste. As a result, proteins like alpha-synuclein build up to toxic levels and contribute to the loss of nerve cells.
Currently, there are no disease-modifying therapies available to treat GBA1-driven Parkinson’s disease. Medications that help improve GCase function could reduce the accumulation of misfolded proteins and improve brain health.
Congruence is using its computational drug discovery engine, Revenir, to study how GBA1 mutations change the structure and function of the GCase enzyme. By analyzing surface features and other biophysical properties of both the mutated and normal proteins, this platform helps identify the defects caused by the mutations and how they might be corrected.
The computational tool has identified regions in the GCase enzyme other than its active site that can help change the protein’s shape and structure, helping to increase its activity, as well as regions that can facilitate the enzyme’s location and function within lysosomes.
After the candidate molecules are optimized, researchers will conduct preclinical experiments in the lab to check whether they are efficient and safe. Based on such experiments, they hope to get approval to start a study in people with GBA-PD disease to see how well selected molecules may help to slow down or stop the disease.
“The Michael J. Fox Foundation supports a broad portfolio of research and drug development around important Parkinson’s disease biology such as GBA1,” said Brian Fiske, PhD, MJFF’s chief scientist, “Congruence’s efforts to advance novel therapies contribute critically to our shared commitment to deliver new treatments for people with Parkinson’s.”
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