CMTR Featured Speakers

CMTR Featured Speakers
23 June, 2019


Rudolf Martini, PhD, University Hospital of Würzburg, Department of Neurology, Developmental Neurobiology, Würzburg, Germany
Title: Pathogenetic Inflammation in Models for Schwann Cell-related Charcot-Marie-Tooth Disorders

   

Previous studies from our laboratory have shown that in models for distinct forms of Charcot-Marie-Tooth neuropathy, phagocytosing macrophages mediate demyelination and perturbation of axons. One important mediator is colony-stimulating factor-1, unexpectedly expressed by endoneurial fibroblasts and essential for macrophage-mediated demyelination, Schwann cell dedifferentiation and axonopathy. Interestingly, macrophage-related inflammation is also a driving force for developing neuropathy in aging nerves. Further activities concerning the basic pathomechanisms are underway to decipher cell-cell communication within the peripheral nerves under disease conditions. As a translational approach, we developed distinct attempts to attenuate macrophage-related peripheral nerve inflammation as putative options to ameliorate disabling symptoms associated with CMT-1. These activities may pave the way for the development of treatment options for Charcot-Marie-Tooth neuropathies, but also for aging nerves.


Charlotte Sumner, MD, Johns Hopkins University School of Medicine, Baltimore, Maryland , United States
Title: Mechanisms of TRPV4-induced Peripheral Nerve Disease

   

Dominant and recessive missense mutations of the cell surface-expressed cation channel transient receptor potential vanilloid 4 (TRPV4) cause CMT2C and distal SMA. As one of the few ion channels associated with peripheral nerve degeneration, TRPV4 represents a promising therapeutic target. We have demonstrated that TRPV4 mutations are clustered in specific intracellular domains of the protein and cause a gain of channel function in cultured cells and in a Drosophila model. This gain of function is associated with altered TRPV4 post-translational modifications and protein-protein interactions. Mice expressing mutant TRPV4 protein show severe neurological deficits that can be reversed by TRPV4 antagonists. Together these data suggest that TRPV4 antagonism could be feasible therapeutic strategy in patients. Preliminary data regarding the cellular mechanisms of disease will be discussed.


CMTR Featured Speakers
24 June, 2019


Jan Senderek, MD, Friedrich-Baur-Institute at the Department of Neurology, LMU Munich
Title: Rare and Genetically Undiagnosed Forms of Inherited Peripheral Neuropathies

Beyond relatively frequent forms of inherited peripheral neuropathies such as sensorimotor Charcot-Marie-Tooth neuropathy related to duplication of the PMP22 gene, many rare or extremely rare subtypes do exist. These IPN forms are often autosomal recessively inherited, can be purely sensory or motor and the disease causing variants are still unknown in many patients. Some of the recently identified genetic defects affect genes, which have been previously linked to syndromic and metabolic disease but not non-syndromic IPN. Conversely, peripheral neuropathy can also be a clinical feature in rare genetic multisystem disorders leading to complex phenotypes. This presentation will give a brief overview on rare and less well-recognized IPN forms and their genetic and pathophysiological basis.


Josh Burns, PhD, The University of Sydney, Sydney, Australia
Title: Measuring Disability of Infants, Children and Adults with CMT

   

Accurate and precise measurement of disease severity and level of disability in patients with inherited neuropathies is crucial for natural history studies and disease-modifying clinical trials. In this talk, I will describe the development, validation and implementation of three clinical outcome assessments for Charcot-Marie-Tooth disease: CMT Infant Scale (CMTInfS), CMT Pediatric Scale (CMTPedS) and CMT Functional Outcome Measure (CMT-FOM).