P0 GLYCOPROTEIN TRAFFICKING AND QUALITY CONTROL IN CMT1B NEUROPATHY

Hereditary neuropathies are a common problem seen in Neurology Clinics, in which the wrapping around nerves that conduct impulses to muscles are damaged. Many neuropathies appear in every generation of a stricken family and unfortunately affect children. Although disease genes have been identified for neuropathies, how disease is caused is poorly understood and there is no effective treatment. Genetic studies of hereditary neuropathies strongly suggest that most do not result simply because the disease gene does not work. Instead the disease gene has a ‘toxic’ effect on the cells in the nerve. In order to understand that toxicity, we study mice containing the mutant genes, that we have already shown produce excellent models of hereditary neuropathies; the mice become weak and have difficulty walking over time. When examined under the microscope, their nerves resemble those of human patients. In these mice, we have shown activation of a pathway that is toxic to the cells in nerve. If we block this pathway genetically, the mouse nerves improve and the mouse can walk normally. In this study, we propose to further study the activation of this pathway, and how its activation may worsen nerve function, and produce a cell culture-based test that can identify potential ‘targets’ for new drugs that could block this toxic pathway and treat hereditary neuropathies.