Casma selects treatment CSM-101 for Gaucher-related Parkinson’s
Company to seek FDA permission in 2026 to start clinical testing in patients
Casma Therapeutics has selected its first experimental therapy candidate, dubbed CSM-101, which will be developed to treat Gaucher’s disease patients who have Parkinson’s disease.
The company is planning to submit an investigational new drug application to the U.S. Food and Drug Administration (FDA) in 2026 asking for permission to start clinical testing in people.
“Our nomination of CSM-101 marks a major milestone for Casma and the field as we translate our deep expertise in … lysosomal biology into therapeutic candidates,” Frank Gentile, PhD, Casma’s CEO, said in a company press release.
Gaucher disease is caused by mutations in the gene GBA1, which provides instructions to make an enzyme called glucocerebrosidase (GCase). This enzyme is normally needed to break down a fatty molecule called glucocerebroside. It is essential for the function of lysosomes, which are like cellular recycling centers that break down molecular waste into simple components that can be reused by the cell.
In Gaucher disease, mutations in the GBA1 gene cause GCase to be missing or dysfunctional, so glucocerebroside builds up to toxic levels in cells.
People with Gaucher disease are at increased risk of developing Parkinson’s disease, which is a neurodegenerative disorder marked by motor symptoms such as tremor, stiffness, and slowness.
The connection between Gaucher and Parkinson’s isn’t totally understood, but it’s thought that lysosomal dysfunction in nerve cells may predispose people with Gaucher to developing Parkinson’s. Lending credence to this idea is that fact that there are certain GBA1 mutations that don’t cause Gaucher disease, but predispose people toward the development of Parkinson’s.
Our preclinical data demonstrate that activating TRPML1 effectively addresses lysosomal dysfunction, a central driver in both rare and prevalent neurodegenerative diseases.
CSM-101 is an oral therapy that’s designed to activate a protein called TRPML1, which helps to control lysosome activity. By activating TRPML1, CSM-101 aims to boost the activity of lysosomes to counteract the dysfunction caused by GBA1 mutations.
“Our preclinical data demonstrate that activating TRPML1 effectively addresses lysosomal dysfunction, a central driver in both rare and prevalent neurodegenerative diseases,” Gentile said.
CSM-101 shown to reach brain at high levels in preclinical models
Casma will first be focused on developing CSM-101 for Gaucher-associated Parkinson’s. The company may then expand to investigate the therapy in Parkinson’s associated with GBA1 mutations and broader Parkinson’s populations.
“By focusing first on genetically defined patient populations and leveraging robust biomarkers, we are positioned to deliver rapid clinical proof of concept with the potential for meaningful benefits for patients,” said Leon Murphy, PhD, chief scientific officer of Casma.
In preclinical models of Gaucher disease, CSM-101 has been shown to reach the brain at high levels, reduce the toxic buildup of fatty molecules, reduce brain inflammation, and improve survival, according to Casma.
The company also reports that CSM-101 has shown promise in preclinical models of Parkinson’s, including by helping to preserve the health of the nerve cells that sicken and die in Parkinson’s.
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