PharmaTher Plans to Develop Ketamine as Potential ALS Treatment

Under an agreement with the University of Kansas, PharmaTher has gained exclusive worldwide rights to develop and possibly commercialize ketamine as a therapy for amyotrophic lateral sclerosis (ALS).

“We are pleased to have added the [ALS] program to our already impressive development pipeline that focuses on novel uses, formulations and delivery of ketamine in the treatment of neuropsychiatric, neurological and neuromuscular diseases,” Fabio Chianelli, PharmaTher’s CEO, said in a press release.

Ketamine is a type of psychedelic or dissociative compound that blocks sensory perception, and is primarily used for starting and maintaining anesthesia. As esketamine, it was approved in 2019 for treatment-resistant depression.

Researchers at the University of Kansas identified ketamine’s potential as an effective ALS treatment. Preclinical research done at the university is reported to have shown that ketamine can preserve muscle function as the disease progresses, potentially increasing life expectancy in ALS patients when given in the early stages of muscle decline.

Ketamine works by lowering cellular D-serine levels, partially activating dopamine receptors, and blocking N-methyl-D-aspartate (NMDA) receptors. Elevated D-serine and low dopamine levels are both associated with ALS.

ALS patients also have higher-than-usual levels of the neurotransmitter glutamate — a chemical messenger used by nerve cells to communicate — in the brain and spinal cord. This creates a prolonged and overwhelming activation of nerve cells that is toxic and damaging.

Part of how glutamate overly  activates nerve cells is mediated through the NMDA receptors, which overload these neurons with calcium. In contrast to Rilutek (riluzole), an NMDA inhibitor and approved ALS treatment, ketamine is thought to indirectly block the NMDA receptor to possibly lessen or prevent glutamate’s toxic effects.

Together, these mechanisms may contribute to ketamine being neuroprotective, which could aid motor neurons damaged over the course of ALS.

Few ALS treatments currently exist, with Radicava (edavarone) being the first new therapy approved in 20 years (in 2017). While current approved medications are effective against ALS mechanisms, PharmaTher notes it its release that they have little measurable effect on slowing disease progression or improving patients’ survival.

Finding more effective treatments is a critical and unmet need for ALS.

PharmaTher also announced plans to file an application with the U.S. Food and Drug Administration (FDA) requesting the right to open a Phase 2 clinical trial of ketamine in ALS patients this year. It is also planning to seek orphan drug status from the FDA, which helps to speed a therapy’s development and testing, in addition to offering the company financial and other support in these efforts.