By Katherine Forsey, PhD | CMTA Chief Research Officer
Current treatments for Charcot-Marie-Tooth disease (CMT) focus mainly on managing symptoms. But new advances in genetic therapies are changing the conversation and offering real hope for the future. CMTA is investing heavily in research that targets the root cause of CMT: the genetic mutations that drive the disease.
I’m putting these therapies under the microscope because they’re going to come up more and more as research advances toward clinical trials. It’s important for all of us to stay informed, so let’s dive in.
What Are Genetic Therapies?
Genetic therapies aim to correct or modify the underlying mutations that cause diseases like CMT. These therapies can work in several ways, including repairing, replacing, turning off, or adjusting how much of a gene is expressed.
You might hear “gene therapy” and “genetic therapies” used interchangeably, but there’s a difference:
- Gene therapy refers specifically to inserting a healthy copy of a gene into cells to replace or compensate for a faulty one.
- Genetic therapy is the broader category. It includes gene therapy, but also tools like gene editing, gene silencing, and RNA-based treatments.
Types of Genetic Therapies
Through CMTA’s Strategy To Accelerate Research (CMTA-STAR), we’re supporting work on a wide range of genetic therapy approaches:
- CRISPR/Cas9 – Molecular scissors that precisely cut and fix faulty DNA. We’re funding CRISPR-based studies at Gladstone Institutes with CMTA-STAR Advisory Board member Bruce Conklin, MD.
- Antisense Oligonucleotides (ASOs) – Synthetic molecules that bind to RNA and block or modify how a gene is read. We’re supporting ASO development at the University of Miami with CMTA-STAR Advisory Board member Mario Saporta, MD, PhD.
- Small Interfering RNA (siRNA) – Silences faulty genes by destroying the RNA before it can make harmful proteins.
- shRNA (short hairpin RNA) – Long-acting RNA therapy that reduces overactive gene expression, like putting a dimmer switch on a gene that’s too “bright.”
- Gene replacement therapy – Delivers a working copy of a gene. CMTA is supporting this approach at the University of Texas Southwestern (UTSW) with researchers Xin Chen, MD, and CMTA-STAR Advisory Board member Steven Gray, PhD.
- Base editing and prime editing – Next-generation tools that rewrite individual DNA letters without cutting the entire strand.
The Big Hurdle: Getting to the Peripheral Nerves
One of the biggest technical challenges in treating CMT is delivery. Most genetic therapies need to reach the peripheral nerves which are long, delicate structures that are difficult to access and are protected by the blood-nerve barrier. Getting therapies past this protective barrier presents significant challenges.
CMTA-funded researchers are exploring multiple delivery strategies, including viral vectors, nanoparticles, extracellular vesicles and direct injection, to get therapies where they need to go.
What’s in the Clinical Trial Pipeline?
Thanks to our CMTA-STAR Alliance Partners, several CMT genetic therapies are moving closer to clinical trials:
- CMT1A – Novartis is developing an ASO. Armatus Bio is using siRNA with an AAV9 vector. Nervosave Therapeutics is exploring shRNA via local injection. Sarepta is working on a gene therapy. All aim to reduce PMP22 overexpression. More than 200 CMTA community members helped shape one of these programs through our Patients as Partners in Research platform.
- CMTX1 (CMT1X/CMTX) – Sarepta Therapeutics is working with CMTA-STAR Advisory Board member Kleopas Kleopa, MD, on a gene therapy to replace the faulty GJB1 gene, with promising animal model results.
- CMT2A and CMT1B – CRISPR-based approaches are showing encouraging signs in early-stage research.
- CMT4C – CMTA and UTSW are collaborating with a patient-led task force to bring an AAV-based gene therapy into an investigator-led trial.
If these strategies succeed, they can be adapted for other types of CMT. Once we solve the delivery challenge, the technology becomes much more widely applicable.
Looking Ahead
Genetic therapies represent a major step forward. They don’t just manage symptoms—they aim to change the course of the disease itself.
While challenges remain, particularly around delivery, CMTA is committed to moving this science forward. We’re hopeful that within the next 5 to 10 years, several of these therapies could enter clinical trials and eventually reach patients.
How You Can Help
This research doesn’t move forward without you.
- Donate to CMTA-STAR to fuel this work.
- Join Patients as Partners in Research to help guide therapy development and be the first to hear about trial opportunities.
Together, we’re changing what’s possible for people with CMT.
Under the Microscope is a quarterly column from CMTA Chief Research Officer Dr. Katherine Forsey, offering an inside look at the science behind CMT research and what it means for the CMT community.
About the Author
Katherine Forsey, PhD, is a trained biologist in the UK, earning her PhD in reproductive biology and IVF. As the CMTA’s Chief Research Officer, she leads CMTA-STAR and oversees the CMTA-STAR Advisory Board, a team of over 30 world-renowned CMT experts who evaluate research projects and help shape CMTA’s scientific strategy. Under her leadership, CMTA-STAR is managing more than 50 active research projects across academic labs and industry collaborations.
Published on: June 30, 2025