Experimental Treatments for Charcot–Marie–Tooth Disease (CMT)

There is no cure for Charcot-Marie-Tooth disease. Nor have scientists come up with any approved therapies to address the underlying causes of the genetic neurological disorder.

A greater understanding of the genes that cause CMT, and how they cause it, has led to researchers beginning to develop therapies that could prevent or treat the disease, however.

The cause of CMT is a gene mutation, and lots of mutations are associated with it. A faulty gene produces an abnormal protein or no protein at all. Sometimes the mutation involves extra copies of a gene, which triggers the over-production of a protein. This leads to a disruption of nerve signals between the brain and muscles, resulting in loss of sensation and weakness, generally starting in the feet.

The severity and progression of CMT depend on what type of mutation patients have. This can affect what treatments work for them.

Researchers are studying genes known to cause the disease and the way that mutations affect them. They are also trying to identify additional genes that cause CMT.

The CMT Association is at the forefront of research into the disease through its STAR program, but other organizations are involved as well.

Understanding CMT

A number of research groups are focusing on increasing scientists’ understanding of CMT and developing ways to diagnose it.

An example is the TREAT-CMT project, a collaboration between 12 research groups in Spain. The project has a range of aims. One is identifying additional mutations that cause CMT. Another is discovering biomarkers that can flag the disease. Yet another is developing cell or animal models of CMT that can be used to test treatments.

Investigational drugs

Several potential CMT therapies are being evaluated in clinical trials.

Pharnext developed PXT3003 to treat people with CMT type 1A, the most common form of the disease. It works by blocking PMP22, a protein whose over-production in some CMT1A patients causes nerve damage.

Phase 2 clinical trials showed PXT3003 to be a promising treatment for CMT1A, and that it was safe. The results were published in Orphanet Journal of Rare Diseases.

The company is also conducting a Phase 3 trial of the therapy. The international, randomized, double-blind, placebo-controlled trial (NCT02579759) is called PLEO-CMT. In addition, it is doing a long-term safety extension study (NCT03023540) of PXT3003 that it has dubbed PLEO-CMT-FU.

Another example of a CMT investigational drug was ACE-083, developed by Acceleron Pharma. Its aim was to improve patients’ strength and muscle mass. After initial positive results in clinical trials, ACE-083 failed to produce significant improvements in quality of life and functional measurements in a Phase 2 trial leading to its discontinuation in 2020.

Regulators have approved Addex Therapeutics’ request to test its CMT1A drug candidate, ADX71441, in clinical trials.

Researchers have tested the therapy’s ability to inhibit the histone deacetylase enzyme in a zebrafish model of CMT2A, the second most common form of CMT. Overactivity of the enzyme is associated with CMT2A.

The work is being done at the University of Sheffield in England, in collaboration with the Hereditary Neuropathy Foundation and Acetylon Pharmaceuticals, a subsidiary of Celgene.

It is important to note that not all clinical trials are successful. For example, researchers investigated whether vitamin C could help CMT patients. Results suggested there was no benefit.

Gene and stem cell therapy

Other approaches that researchers are taking to developing treatments for CMT are gene therapy and stem cell therapy.

Gene therapy involves delivering a functional copy of a gene that is faulty in the disease. Stem cell therapy involves delivering healthy cells to promote nerve regeneration.

Researchers have conducted studies of these approaches, but neither technique has advanced to the clinical trial stage.

In a study of a mouse model of CMT1A, researchers used a virus to deliver a functional version of the NT-3 gene. That gene is involved in the survival of Schwann Cells, which maintain the protective myelin sheath that surrounds nerves. Delivering a functional gene appeared to promote nerve regeneration.


Charcot Marie Tooth News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.