Introduction: Charcot-Marie-Tooth disease (CMT) and related neuropathies represent the most prevalent inherited neuromuscular disorders. Nonetheless, there is still no pharmacological treatment available for any CMT type. However, the landscape is rapidly evolving and several novel approaches are providing encouraging results in preclinical studies and leading to clinical trials.Areas covered: The authors review the most promising therapies under study and the ongoing/planned clinical trials. Several approaches to address PMP22 overexpression underlying CMT1A, the most frequent subtype, are being tested. Gene silencing, targeting PMP22, and gene therapy, to introduce specific genes or to substitute or modulate defective ones, are being experimented in animal models. Compounds acting on ER stress, unfolded protein response, neuregulin pathways, phosphoinositides metabolism, axonal transport and degeneration, inflammation, polyol pathway, deoxysphingolipid metabolism, purine nucleotide pool are potential therapeutic candidates for different forms of CMT and related neuropathies.Expert opinion: We are getting closer to find effective therapies for CMT, but are far behind the exciting examples of other genetic neuromuscular disorders. The authors analyze the possible reasons for this gap and the way to fill it. Preclinical and clinical research is ongoing with coordinated efforts and they are confident that in the next few years we will see the first effective treatments.
Keywords: Axonal transport; Charcot-Marie-Tooth disease; Hsan; clinical trials; dHMN; gene therapy; management; myelin; outcome measures; therapy.