Charcot-Marie-Tooth disease type 1 - Molecular pathogenesis to gene therapy

Charcot-Marie-Tooth disease type 1 (CMT1) is caused by mutations in the per ipheral myelin protein, 22 kDa (PMP22) gene, protein zero (PO) gene, early growth response gene 2 (EGR-2) and connexin-32 gene, which are expressed in Schwann cells, the myelinating cells of the peripheral nervous system, Alt hough the clinical and pathological phenotypes of the various forms of CMT1 are similar, including distal muscle weakness and sensory loss, their mole cular pathogenesis is likely to be quite distinct. In addition, while demye lination is the hallmark of CMT1, the clinical signs and symptoms of the di sease are probably produced by axonal degeneration, not demyelination itsel f. In this review we discuss the molecular pathogenesis of CMT1, as well as approaches to an effective gene therapy for this disease.