Groundbreaking genome-editing technique holds promise for treating Charcot–Marie–Tooth disease

Scientific advances over the past century have dramatically changed our world. For example, the world of genetics opens the door to countless possibilities: enhancing human capabilities, treating disease, and even changing the course of evolution.

In a study published last month Communication MedicineResearchers at Tokyo Medical and Dental University (TMDU) have unveiled a breakthrough genome-editing technology. The innovation holds promise for treating peroneal muscular atrophy (CMT), a relatively common genetic neurological disease affecting the nerves for which there is currently no clinical treatment.

CMT is characterized by altered sensation and muscle weakness in the limbs and affects 10 to 80 per 100,000 people. The most common subtype of CMT, known as CMT1A, is caused by a duplication of the gene encoding peripheral myelin protein 22 (PMP22), resulting in higher levels of this protein in affected individuals. PMP22 is important for forming the building blocks of myelin, a fatty insulator that allows signals to travel quickly from the limbs to the brain and back.

Researchers have tried using different techniques to reduce PMP22 in animal models of CMT1A, but have not been successful in translating this to human patients.This may be because existing animal models do not have human-like abilities PMP22 Gene duplication. This study aims to address this issue.

We created the cell model by taking cells from CMT1A patients and growing them into Schwann cells (the cells that make myelin). We then used a specialized genome-editing technology called an AAV vector to reduce the amount of PMP22 protein produced by the cells.

Hitoshi Okazawa, Ph.D., senior author of the study

Because both higher and lower PMP22 levels can lead to different types of neurological disorders (called neuropathies), researchers must be very careful to reduce the extent of PMP22. They created and experimented with different AAV vectors, eventually settling on one that could remove 20 to 40 percent of the virus. PMP22 Gene copies from the genome. This was sufficient to reverse many CMT-related changes in Schwann cell cultures and improve the myelination capacity of these cells, highlighting the potential of this treatment as a clinical treatment for the disease.

“However, there are some issues that need to be resolved before we can introduce this therapy into clinics,” Dr. Okazawa said. “The optimal injection site to reach Schwann cells remains unknown, and the timing of injection may be important and needs study.”

Researchers are cautiously optimistic as similar AAV-based gene therapies begin to gain FDA approval for treating blood disorders. They believe their treatment is low-risk for human use and may be relatively simple to translate into clinical therapies.Given that there are currently no treatments for CMT other than physical therapy, occupational therapy and pain management, the development of this genome editing technology PMP22 This is an important breakthrough that may reduce symptoms and improve quality of life for CMT patients.


Tokyo Medical and Dental University

Journal reference:

Yoshioka, Y., et al.. (2023). AAV-mediated editing of PMP22 rescues peroneal muscular atrophy type 1A features in patient-derived iPS Schwann cells. Communication Medicine.

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