Animal Models and Therapeutic Prospects for Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth (CMT) neuropathies are inherited neuromuscular disorders caused by a length-dependent neurodegeneration of peripheral nerves. More than 900 mutations in 60 different genes are causative of the neuropathy. Despite significant progress in therapeutic strategies, the disease remains incurable. The increasing number of genes linked to the disease, and their considerable clinical and genetic heterogeneity render the development of these strategies particularly challenging. In this context, cellular and animals models provide powerful tools. Efficient motor and sensory tests have been developed to assess the behavioral phenotype in transgenic animal models (rodent and fly). When these models reproduce a phenotype comparable to CMT, they allow therapeutic approaches and the discovery of modifiers and biomarkers. In this review, we describe the most convincing transgenic rodent and fly models of CMT and how they can lead to clinical trial. We also discuss the challenges that the research, the clinic, and the pharmaceutical industry will face in developing efficient and accessible treatment for CMT patients. Ann Neurol 2013;74:391-396