CMTRF/AcuraStem Partnership Yields Promising CMT2A Therapy

In a research partnership with the CMT Research Foundation (CMTRF), a prospective treatment being developed by AcuraStem for amyotrophic lateral sclerosis (ALS) was found to be a promising preclinical therapy candidate for a form of Charcot-Marie-Tooth (CMT) disease.

In the collaborative drug screen for CMT2A, the preclinical small molecule called AS-1 showed improved cell survival, precipitating identification of the compound as a drug prospect.

CMT2A is the most common subtype of CMT2, which accounts for about one-third of CMT cases. The progressive genetic disease, which affects about 5 percent of roughly 3 million CMT patients, is caused by dominantly inherited mutations in the MFN2 gene. Like ALS, CMT2A causes the degeneration of muscle-controlling nerve cells.

The discovery of the effect of AS-1 occurred amid the first phase of a milestone-based partnership established in December 2018 to test thousands of compounds for possible CMT2A treatments. All goals were met, including creation of a neuronal cell line from a CMT2A patient; testing the neurons for CMT2A characteristics, including survival deficit; and showing that the cell line improves cell survival when exposed to nerve cell-supporting neurotrophic factors.

“To be clear, this is the first step on a very long and difficult search for a cure for CMT2A, but it is a very positive first result,” Susan Ruediger, CMTRF’s co-founder and CEO, said in a press release. The CMTRF seeks to find CMT treatments and cures.

Now, scientists will screen all treatments approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) to search for treatments and cures active in patient neurons. The process is expected to speed the process of ruling in — or out — prospective therapeutics, and will use AcuraStem’s iNeuroRX platform. The platform uses living motor neurons derived from patients and validated in animal models to identify and develop new treatments.

“Using FDA/EMA-approved drugs, which have already undergone rigorous clinical trial testing and have a documented positive safety and tolerability profile, we could potentially shorten the time to regulatory approval of one of these drugs as an available treatment option for CMT,” Ruediger said. “Although formulation or dosing of any of these drugs may need to be modified for CMT, the first hurdle to approval — safety — has already been crossed. These drugs potentially could be fast-tracked to the clinic, either alone or in combination.”