With CMTA support of $448,748, researchers are making significant progress in the development of gene editing therapies for CMT1A and CMT1B, the two most common types of demyelinating Charcot-Marie-Tooth disease (CMT). This work is part of a global research collaboration supported by CMTA’s Strategy To Accelerate Research (CMTA-STAR) and aims to address the genetic root causes of these subtypes.
CMT1A is caused by a duplication of the PMP22 gene, which leads to too much PMP22 protein and disrupts the health of Schwann cells. CMT1B is caused by mutations in the MPZ gene, which also impair Schwann cell function. Schwann cells are essential for forming and maintaining myelin, the protective covering that surrounds peripheral nerves. When Schwann cells are damaged, the result is a progressive loss of myelin, leading to muscle weakness, sensory problems, and motor difficulties.
At the University of Wisconsin–Madison, CMTA-STAR Advisory Board Chairperson John Svaren, PhD, and his team have been working to identify regions within the PMP22 gene that control how much protein it produces. Their research has mapped key regulatory elements that can potentially be targeted with CRISPR gene editing. The goal is to reduce PMP22 protein levels in people with CMT1A while leaving the healthy gene copy untouched. These findings offer a promising path forward for the development of allele-specific editing approaches that could one day help restore balance in Schwann cells and reduce disease symptoms.
In Milan, Italy, CMTA-STAR Advisory Board member Maurizio D’Antonio, PhD, and his team at Ospedale San Raffaele are focusing on the MPZ gene and how to correct the damage caused by specific disease-causing mutations. In the first phase of their study, the team used cells from a mouse model of CMT1B to screen several different CRISPR tools. These tools are now being tested in nerve tissue samples to evaluate how well they edit the mutated gene and whether they help improve myelination. The goal is to develop highly targeted gene editing strategies that repair the damaged MPZ gene without affecting the normal copy, offering a more precise and durable therapeutic option than earlier approaches like RNA interference or antisense therapies.
Both research teams are working to overcome a central challenge in gene editing for CMT: how to target only the mutated gene copy without disrupting the healthy one. The findings from these studies are helping to define that balance with greater precision, using CRISPR-based tools that could ultimately lead to treatments with fewer side effects and longer-lasting benefits.
While gene editing is not yet available in the clinic, this research marks an important step toward making that future possible. By investing in early-stage discovery and building a foundation for clinical translation, CMTA-STAR is helping accelerate progress toward treatments that directly address the causes of CMT.
CMTA will continue to share updates as this work advances. The progress made by these research teams offers real hope and serves as a clear reminder that every discovery moves us closer to a future without CMT.
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Published on: July 31, 2025