RNA therapy: a new approach to treat Charcot-Marie-Tooth

The Neuro is one of only 3 sites worldwide with a new clinical trial that hopes to halt the progression of the disease

 February 26, 2026 || by Sophie Lorenzo

Charcot-Marie-Tooth Disease (CMT) has the distinction of being more common in Canada than either Cystic Fibrosis or Myasthenia Gravis while still remaining lesser known. There is currently no treatment or cure for CMT, the most common inherited neuropathy.

That’s why the Clinical Research Unit at The Neuro (Montreal Neurological Institute Hospital) is proud to be one of only three sites worldwide offering a clinical trial for a potential new RNA treatment that aims to stop the progression of this genetic condition.

“This trial is particularly exciting because it will study a form of genetic therapy that directly targets the mechanism of the disease. That is not something that has been done before for CMT. Most treatments aim to slow progression. If we could completely stop the disease, that would be a big win,” explains Rami Massie, MD, a neurologist and one of the principal investigators for neuromuscular trials at The Neuro.

Understanding Individual Progression

CMT is actually a group of inherited, progressive genetic disorders that cause damage to peripheral nerves, affecting muscles in the legs, feet, hands, and arms. According to the Hereditary Neuropathy Foundation of Canada, CMT affects one out of every 2,500 people. It leads to numbness, weakness and the loss of fine motor skills slowly worsening over time. Individuals may require orthotics and braces, physical and occupational therapies, as well as surgery to maintain their quality of life.

In the most common form, CMT Type 1, the protective myelin sheath surrounding axons—the long nerve fibres responsible for transmitting electrical signals—gradually deteriorates. When myelin is impaired, nerve signals slow or fail entirely.

“The disease can present with different severities and progress at different rates. Most individuals are diagnosed by their early 20s, but there can be a huge discrepancy. Some people won’t notice symptoms until they’re in their 40s, while others have symptoms starting in childhood,” says Massie.

Targeting the Right Protein

The majority of CMT1 cases are caused by a duplication of the PMP22 gene, which provides instructions to make a protein called peripheral myelin protein 22. The duplication causes the body to generate an excess of RNA, which becomes toxic and leads to cell degeneration.

“This potential treatment is designed to match the specific mRNA that instructs cells to produce the PMP22 protein. Hopefully, this will reduce the amount of toxic mRNA so that cells produce less of the protein, bringing it down closer to normal levels,” explains Dr. Massie.

Towards a Disease‑modifying Therapy

“It’s exciting because two other inherited neuropathies used a similar RNA treatment and it was very effective. If the treatment in this clinical trial shows similar results, this would be the first disease-modifying therapy for CMT1. The hope is that one day, we could treat patients who have the genetic variant before they even develop symptoms,” Massie concludes.

For more information, contact the Neuromuscular trials team at The Neuro’s Clinical Research Unit: nm.neurocru@mcgill.ca, or visit cru.mcgill.ca/nm.