CMTA puts $200,000 behind CMT2A gene therapy tools

The Charcot-Marie-Tooth Association is funding a 24-month project at UC San Diego to test antisense oligonucleotide candidates for CMT2A using a patient-derived discovery platform. The work aims to identify a selective therapy for a currently untreatable form of Charcot-Marie-Tooth disease and create a blueprint for future allele-selective treatments.

Why it matters: - Charcot-Marie-Tooth disease type 2A, or CMT2A, currently has no approved treatment. - The new project could move an antisense oligonucleotide, or ASO, candidate closer to later-stage preclinical development. - The work also could show how CMTA-funded tools can speed up allele-selective therapies for CMT.

What happened: - The Charcot-Marie-Tooth Association announced a $200,000 investment through its Strategy to Accelerate Research, or CMTA-STAR. - The grant funds a 24-month project led by Uri Manor, PhD, adjunct associate professor of cell and developmental biology at UC San Diego. - The project will use a CMTA-funded patient-derived discovery platform to develop and test ASO candidates for CMT2A.

The details: - The project builds on CMTA-STAR Preclinical Toolbox resources created in a previous CMTA-funded project in the Manor Laboratory. - Those resources include a CMT2A patient-derived cell platform spanning fibroblasts and iPSC-derived motor neurons. - The toolbox also includes a CMTA-created CMT2A rat model, which will serve as the future in vivo bridge. - Together, the cell platform and rat model create a path from human cells to animal testing to judge whether an ASO candidate is ready for further preclinical development. - Dr. Manor said the goal is to selectively reduce the disease-associated message, preserve the healthy copy as much as possible, and advance only candidates that show measurable rescue of nerve-cell function. - Katherine Forsey, PhD, CMTA chief research officer, said the project uses a toolbox resource CMTA funded for CMT2A to test treatments in the patient-derived nerve cells damaged by the disease. - A successful outcome would identify a selective ASO candidate for CMT2A. - The project could also provide a practical blueprint for using CMTA toolbox models to advance allele-selective therapies for CMT. - CMTA says it has invested more than $33 million since 2008 to accelerate research toward new treatments and a cure. - CMTA describes itself as the leading nonprofit organization dedicated to improving the lives of people living with CMT. - CMTA is the largest philanthropic funder of CMT research.

Between the lines: - The announcement shows a shift from building research tools to using those tools on a specific therapeutic pipeline. - CMTA is betting that early investment in disease models can shorten the path from lab work to treatment-ready candidates. - The strategy also reflects a broader push to pair patient-derived cells with animal models before committing to deeper preclinical work.

What's next: - The 24-month project will test ASO candidates in the patient-derived cell platform and then move the strongest options toward in vivo validation. - Researchers will look for a candidate that can selectively target the disease-causing message while limiting effects on the healthy copy. - If the effort works, CMTA could have a reusable framework for future CMT therapeutic programs.

The bottom line: - CMTA is using its own research infrastructure to try to turn CMT2A from a modeling challenge into a treatment pipeline. - More information: cmtausa.org