Intra-molecular compound advanced as potential disease-modifying therapy for ALS

A Cincinnati-based life sciences company announced that one of its development candidates, ASHA-624, will be advanced as a potential disease modifying therapy for amyotrophic lateral sclerosis.

According to a release from Asha Therapeutics, the novel therapy is also planned additional indications in chemotherapy-induced peripheral neuropathy, glaucoma, traumatic brain and spinal cord injuries.

ASHA-624 is an intra-molecular glue compound that rearranges the normal biology of SARM1 — a protein that promotes axonal degeneration and neurodegeneration — by “gluing” the activated form of the protein into an inactive one that leads to neuroprotection by prevention of axon and neuron loss, according to Asha. In ALS, SARM1 activation leads to axonal loss, neurodegeneration and ultimately motor dysfunction.

In preclinical models, ASHA-624 was shown to reverse motor impairment and dysfunction to similar levels as healthy controls while placebo treated groups exhibited continual and significant motor function decline.

“Nomination of ASHA-624 as a development candidate for clinical translation in ALS, alongside Asha’s previously nominated ASHA-091 compound with indications in Alzheimer’s disease, Parkinson’s disease and ALS, is a key juncture for Asha in supporting our mission of providing novel modifying therapies for conditions with current treatment options limited largely to symptomatic standard of care,” Bradlee Heckmann, PhD, co-founder and chief scientific officer of Asha, in the release.