Neurotrophin-3 therapy for Charcot–Marie–Tooth disease type 1A

Charcot–Marie–Tooth disease type 1A (CMT1A), a common inherited peripheral neuropathy (estimated prevalence 1 in 7,000 to 8,000), is caused by intrachromosomal duplication of a 1.4-megabase segment of chromosome 17p12. This large segment of duplicated DNA contains more than 20 genes, for each of which CMT1A patients have three copies, rather than the normal two.¹ However, the excess copy number of only one of these genes, peripheral myelin protein 22 (PMP22), seems to be responsible for all of the phenotypic features of CMT1A. Thus, rodents engineered to express multiple additional copies of the PMP22 gene, and hence to synthesize excess amounts of PMP22 protein, develop widespread peripheral nervous system (PNS) segmental demyelination and distal PNS sensorimotor axonopathy closely resembling the PNS pathology seen in patients with CMT1A.² PMP22 is a Schwann cell transplasma membrane protein that, by virtue of adhesive interactions with the principal myelin glycoprotein, P0, contributes to the organization and stabilization of compact myelin.³ Important recent evidence in support of a cause-and-effect relationship between excess PMP22 protein expression in CMT1A was provided by …