Modulating Neuregulin-1 Signals to Treat Hereditary Demyelinating Neuropathies

Demyelinating hereditary neuropathies are a group of common diseases, due to problems in the fatty insulating sheath that surrounds nerves. They result in muscle weakness, altered sensation and pain. These neuropathies can affect children, all generations in a family, can be severe and shorten lifespan. Many genes causing neuropathies have been identified, along with the notion that they cause disease by different mechanisms. For this reason there is not effective therapy yet, and it is difficult to envision a common therapeutic strategy for all hereditary neuropathies. Recently however the Coordinator of this consortium discovered a growth factor that increases the amount of myelin that nerves make. Better yet, this factor's effect can be increased or decreased by using drugs that have already been tested in clinical trials for other diseases. The coordinator teamed up with other groups working in the San Raffaele Institute in Milan, Italy. These investigators have been working for years in hereditary neuropathies, and contributed to the discovery of genes, to understand how they work and to generate animal models of the diseases. The group include clinicians who cure neuropathic patients, collect biopsies, generate human stem cells for fragments of patient's skin, and experiment new biomaterials that enhance nerve regeneration and myelination. By joining together all of these resources, our group is now planning to test the drugs that modulate the pro-myelinating growth factor in cellular models, including human adult stem cells from patients, to optimize their function; and also in animal models of the diseases and together with the new biomaterials, to test their efficacy. We expect that these studies will show us if these drugs, already in use in patients, can cure hereditary neuropathies.