Charcot-Marie-Tooth disease: electrophysiology, molecular genetics and clinical management.

Over the past decade there has been a huge increase in the understanding of the molecular basis of Charcot-Marie-Tooth disease (CMT). Additionally there has been a better delineation of the neurophysiological deficits and clinical problems associated with CMT. This paper reviews the current molecular basis of CMT and the electrophysiological, clinical and phenotypical characteristics of the various subtypes, followed by a discussion of novel and promising therapeutic interventions that potentially could be used as part of a treatment regimen for CMT. These interventions may involve attempts to slow down or stop neurodegenerative processes through nerve growth factors, limiting oxidative stress by using antioxidants, or normalizing gene expression through genetic manipulation. Other potential therapeutic target areas include the progesterone receptor on myelin-forming Schwann cells, the immune system via modulation of nerve inflammation, and enhancing glutathione transferase activity. While ongoing molecular research continues to identify more of the mutant genes and proteins that cause the various disease subtypes, the focus of clinical research should continue to be on developing pharmaceutical and rehabilitative therapies to reverse nerve degeneration and ultimately improve the functioning of people with CMT.