Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.
Department of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima 890-8544, Japan.
Genes (Basel). 2023 Jul 1;14(7):1391. doi: 10.3390/genes14071391.
Charcot-Marie-Tooth disease (CMT) and associated neuropathies are the most predominant genetically transmitted neuromuscular conditions; however, effective pharmacological treatments have not established. The extensive genetic heterogeneity of CMT, which impacts the peripheral nerves and causes lifelong disability, presents a significant barrier to the development of comprehensive treatments. An estimated 100 loci within the human genome are linked to various forms of CMT and its related inherited neuropathies. This review delves into prospective therapeutic strategies used for the most frequently encountered CMT variants, namely CMT1A, CMT1B, CMTX1, and CMT2A. Compounds such as PXT3003, which are being clinically and preclinically investigated, and a broad array of therapeutic agents and their corresponding mechanisms are discussed. Furthermore, the progress in established gene therapy techniques, including gene replacement via viral vectors, exon skipping using antisense oligonucleotides, splicing modification, and gene knockdown, are appraised. Each of these gene therapies has the potential for substantial advancements in future research.
遗传性周围神经病（CMT）及其相关神经病是最主要的遗传性神经肌肉疾病；然而，尚未确立有效的药物治疗方法。CMT 具有广泛的遗传异质性，影响外周神经并导致终身残疾，这对全面治疗的发展构成了重大障碍。据估计，人类基因组中的大约 100 个基因座与各种形式的 CMT 和相关遗传性神经病有关。本综述深入探讨了最常见的 CMT 变异体（即 CMT1A、CMT1B、CMTX1 和 CMT2A）所采用的有前景的治疗策略。正在临床和临床前研究的 PXT3003 等化合物以及广泛的治疗剂及其相应机制均进行了讨论。此外，还评估了已建立的基因治疗技术的进展，包括病毒载体的基因替换、反义寡核苷酸的外显子跳跃、剪接修饰和基因敲低。这些基因治疗方法中的每一种都有可能在未来的研究中取得重大进展。
