With CMTA support of $300,000, CMTA Strategy To Accelerate Research (CMTA-STAR) Advisory Board member Bruce Conklin, MD, and his team at The Gladstone Institutes are developing a CRISPR-based strategy to treat CMT2A, which is caused by mutations in the MFN2 gene. Instead of creating a separate treatment for each of the more than 200 known MFN2 mutations, the team is pursuing an allele-specific approach (a way to target only the faulty copy of a gene while leaving the healthy copy untouched) designed to remove the faulty copy of the MFN2 gene while leaving the healthy copy intact, a method expected to benefit many patients regardless of their exact mutation.
September 2025 Update
In the first phase of this work, researchers are applying a high-throughput screening method called Color-seq (a rapid test that lets them check thousands of gene-editing options at once) to evaluate more than 10,000 CRISPR guide RNA pairs (the “address labels” that tell CRISPR where in the gene to make a cut) in human nerve cells derived from stem cells. The top candidates are then validated in engineered human cell lines carrying common MFN2 mutations (lab-grown cells designed to mimic the disease) to confirm their ability to restore normal nerve function.
This project is addressing critical technical barriers to applying gene editing in CMT2A and is on track to establish a roadmap for allele-specific CRISPR therapies. By advancing this novel editing strategy, the Conklin team is laying the groundwork for future clinical translation and creating a template that could be adapted to other forms of CMT.
