Charcot-Marie-Tooth disease (CMT) is the commonest form of inherited neuropathy and has an incidence of 1/2500. CMT1A is the commonest subtype of CMT, which is caused by duplication of peripheral
myelin protein 22 (PMP22) gene and accounts for approximately 50% of CMT diagnosed by genetic testing. Duplication of PMP22 may influence the production of PMP22
mRNA and
protein, and interfere with the proliferation, differentiation and apoptosis of Schwann cells. In addition, deregulation of NRG1/ErbB pathway and lipid metabolism can also lead to dysfunction of Schwann cells. Such factors may disturb the myelination process, leading to axon degeneration,
muscle weakness, and
atrophy subsequently. Accordingly,
drug therapies for CMT1A are developed by targeting such factors. PXT3003,
antisense oligonucleotides (ASOs) and
small interfering RNA (
siRNA) are supposed to down-regulate the level of PMP22
mRNA, while recombinant human NRG-1 (rhNRG1) and neurotrophin-3 (NT-3) may enhance Schwann cells survival and differentiation. In addition,
lipid-supplemented diet may remedy the defect of lipid metabolism and maintain the proper structure of myelin. Other targeting drugs include
ascorbic acid,
progesterone antagonists, IFB-088,
ADX71441, and ACE-083. This review is to sum up the pathogenesis of CMT1A and promising targeting
drug therapies for further research.