CMT Research Foundation Chief Science Officer Grace Pavlath, PhD comments on recent work by Morelli et al: Allele-specific RNA interference prevents neuropathy in Charcot-Marie-Tooth disease type 2D mouse models
Some types of CMT result from the expression of a mutant protein which is toxic to the peripheral nervous system. One approach to treating these subtypes of CMT would be to target and eliminate the messenger RNA (mRNA) responsible for the production of the mutant protein. Importantly, such a therapeutic strategy must leave the mRNA encoding for the normal version of the protein intact so adequate amounts of normal protein are available for peripheral nerve function. The work by Morelli et al is the first time this goal has been achieved in any form of CMT. These researchers used a gene therapy approach to target mutant mRNA for the protein GARS in two mouse models of CMT2D and almost completely prevented the neuropathy in mice treated at birth. The effects persisted for at least one year. Delaying treatment until after disease onset in the mice showed modest benefit and this effect decreased the longer treatment was delayed. Further work is required before such a therapeutic strategy is ready for testing in humans. Learn more here.
by Grace Pavlath, PhD, Chief Science Officer for the CMT Research Foundation