MJFF grants totaling $7.6M will help Casma develop Parkinson’s therapy
Goal: Validate CSM-101's target and get treatment into first-in-human trials
Written by |
- Casma Therapeutics was awarded $7.6 million in two grants from The Michael J. Fox Foundation for Parkinson's Research to develop its treatment candidate CSM-101.
- The funding supports research efforts to validate CSM-101's target and to advance the therapy to human clinical trials.
- In mouse models, the therapy extended survival and reduced neuroinflammation.
Casma Therapeutics has been awarded $7.6 million from The Michael J. Fox Foundation (MJFF) to support the preclinical development of its CSM-101 therapy candidate for Parkinson’s disease.
The funding includes a $2.1 million grant under the Targets to Therapies Initiative, which will be used for helping validate TRPML1 — the protein activated by CSM-101 — as a therapeutic target for Parkinson’s disease. Another $5.5 million grant was awarded under the Therapeutics Pipeline Program to support studies advancing CSM-101 into first-in-human clinical trials.
“These awards reflect strong external confidence in both the relevance of TRPML1 as a therapeutic target and our disciplined approach to advancing CSM-101 to the clinic,” Frank Gentile, PhD, Casma’s CEO, said in a company press release announcing the two grants from the MJFF.
“By supporting translational biomarkers and [investigational new drug (IND)]-enabling studies in parallel, this funding allows us to advance CSM-101 toward the clinic with a high level of scientific and regulatory rigor,” Gentile said.
A progressive disease, Parkinson’s is marked by the continuing loss of dopaminergic neurons, the nerve cells that produce dopamine, a signaling molecule that neurons use to communicate. A hallmark feature of Parkinson’s is the accumulation of toxic clumps of misfolded alpha-synuclein protein, which is thought to drive neuronal damage that causes the disease’s motor symptoms.
Mutations in the GBA1 gene, a known risk factor for Parkinson’s, result in the production of faulty GCase, an enzyme essential for the function of lysosomes, the cells’ recycling centers. This contributes to alpha-synuclein buildup.
CSM-101 showed promise in Parkinson’s mouse model
CSM-101 is an oral small molecule therapy that activates the calcium channel TRPML1, a key regulator of lysosomal function and autophagy, a process in which cells deliver waste to lysosomes to be broken down and recycled. Boosting autophagy may reduce the toxic buildup of alpha-synuclein, according to researchers.
Preclinical studies using a mouse model of Parkinson’s have shown that treatment with CSM-101 improved survival in the animals. It also reduced neuroinflammation, lowered alpha-synuclein levels, and preserved dopaminergic neurons.
The Targets to Therapies grant, called “Development of in Vivo Biomarkers for TRPML1 Target Engagement and Analysis of Therapeutics,” will further support the validation of TRPML1 as a treatment target and evaluation of biomarkers of TRPML1 and lysosomal activation.
The “CSM-101 TRPML1 Agonist for Parkinson’s Disease” project, funded under the Therapeutics Pipeline Program, will evaluate the safety of CSM-101 in preclinical studies. These IND-enabling studies — preclinical investigations required to demonstrate a drug candidate’s safety and effectiveness in animals before launching human trials — aim to identify the dose range for use in future clinical testing.
Following the successful completion of these studies, CSM-101 is slated to be administered to healthy volunteers and people with Parkinson’s as part of a Phase 1 safety and tolerability trial. Also, TRPML1 biomarkers will be established for use in the trial.
Shalini Padmanabhan, PhD, senior vice president of discovery and translational research at MJFF, noted that the foundation “supports research that advances understanding of the biological pathways underlying Parkinson’s disease.” As in this case, the MJFF’s work often entails a two-pronged strategy.
“Through two complementary investments, one focused on strengthening confidence in target biology and biomarker development and another supporting IND-enabling studies, we aim to address key translational gaps and enable more informed evaluation of emerging therapeutic strategies for Parkinson’s disease,” Padmanabhan said.
The company, which is also developing CSM-101 for Gaucher disease, had previously received a $370,000 grant from MJFF that supported Casma’s development of TRPML1 activators for Parkinson’s.
Casma will present preclinical results at two upcoming conferences: the International Conference on Alzheimer’s and Parkinson’s Diseases and related neurological disorders, held in March. 17-21 in Copenhagen, Denmark, and the American Academy of Neurology Annual Meeting, held April 18-22 in Chicago.
