With CMTA support of $110,500, researchers at La Jolla Labs, INC, working with CMTA Strategy to Accelerate Research (CMTA-STAR) Advisory Board Chair John Svaren, PhD, are developing an antisense oligonucleotide (ASO) as a potential treatment for CMT2A. The project aims to increase expression of the mitofusin 1 (MFN1) gene in peripheral nerve neurons as a way to compensate for the damaging effects of disease-associated mitofusin 2 (MFN2) mutations.
ASOs are a type of medicine that can change how a gene works. They work by finding a specific message from a gene inside a cell and turning that message up or down. In this project, La Jolla Labs is developing an ASO that turns up the MFN1 message, helping cells produce more MFN1 protein.
The MFN2 mutations that cause CMT2A damage peripheral nerve neurons, leading to progressive muscle weakness, loss of sensation, and increasing challenges with strength and mobility. Although MFN1 is closely related to MFN2, published research shows that neurons affected by CMT2A naturally produce little to no MFN1. Increasing MFN1 expression could give these neurons another way to perform some of the functions disrupted by faulty MFN2.
The team will design and test ASO candidates that increase MFN1 expression and determine whether increasing MFN1 can compensate for mutant MFN2 and restore cellular function. The goal is to establish whether this approach has the potential to advance toward further therapeutic development for CMT2A.
