# The current status of Charcot-Marie-Tooth disease type 1 A treatment

## TL;DR

This paper reviews current and emerging treatments for CMT1A, a genetic disorder causing nerve damage, with a focus on new drugs and gene therapies.

## Contribution

The paper provides an updated review of therapeutic strategies, including recent clinical and preclinical advances for CMT1A.

## Key findings

- PXT3003 has shown phase III clinical efficacy in reducing CMT1A symptoms.
- Gene editing and iPSC-based therapies show promise but face challenges like off-target effects.
- Current treatment remains supportive, with no disease-modifying therapies yet approved.

## Abstract

Charcot-Marie-Tooth disease type 1 A (CMT1A) is the major subtype of hereditary peripheral neuropathies and arises from a 1.5 megabase (Mb) tandem duplication in chromosome 17p11.2-p12 that contains the complete peripheral myelin protein 22 (PMP22) gene. Patients commonly present with progressive weakness and atrophy of the distal muscles, accompanied by hyperalgesia, decreased or absent tendon reflexes, and foot deformities. Current clinical management relies on multidisciplinary supportive care. Recent preclinical studies targeting potential therapeutic strategies for CMT1A have focused on correcting the gene-dose imbalance of PMP22. Notably, PXT3003 has shown phase III clinical efficacy in relieving symptoms and reducing neuropathy, and is expected to be the earliest CMT1A-targeted drug on the market. Gene editing approaches have also shown therapeutic promise in animal models, but off-target effects remain a concern. In addition, the rapid development of induced pluripotent stem cell (iPSC) technology has paved the way for stem cell therapies, which may be a promising therapeutic approach. This article reviews the existing literature on therapeutic strategies for CMT1A and aims to provide a valuable reference for the clinical treatment of CMT1A.

The online version contains supplementary material available at 10.1007/s13760-025-02881-1.