By: Keith Fargo, PhD, Chief Scientific Officer

We are happy to report that a CMTRF-funded project designed to test a PIKfyve inhibitor in CMT4B1, a particularly devastating form of the disease, has passed the first stage and is moving on to the next stage, a preclinical trial in CMT4B1 model mice.

Before the project even started, the biotech partner, AcuraStem, provided an upgraded version of the drug candidate with superior characteristics, including higher potency and reduced clearance. The first stage of the project included several necessary steps to prepare for the preclinical trial in mice. First, the drug candidate had to be tested in cells in a dish to ensure that it interacted with its intended target, PIKfyve, within cells. Next, target engagement had to be tested in the nerves of healthy mice to ensure that the drug candidate would travel to the tissue of interest and interact with PIKfyve in that environment. Furthermore, Dr. Bolino and her team at Ospedale San Raffaele in Milan also performed checks for toxicity and dose ranging experiments.

The drug candidate passed all tests in stage one – target engagement was observed both in cells in a dish and in healthy mice, no toxicity signals were seen, and a range of doses were found that are expected to be safe and effective in the preclinical trial, which is stage two of the project. Stage two, the final stage, is now set to begin. We look forward to keeping you informed of the progress.

The CMT Research Foundation is committed to finding effective treatments and cures for ALL types of CMT, including rare forms such as CMT4B1. Moreover, if this therapeutic is found to be safe and effective, it may also have utility in other forms of CMT that are characterized by myelin outfoldings, including CMT4B2, CMT4B3, CMT4C, and CMT4H.

Learn more about this project and all the research we fund.