The inherited neuropathy consortium (INC) will investigate Charcot-Marie-Tooth disease (CMT), a heterogeneous group of inherited neurological disorders affecting ~1 in 2,500 people [1, 2]. Over the last 2 decades there have been major advances in identifying the causative genes for CMT with >30 genes already described. These are typically grouped into dominantly inherited demyelinating neuropathies (CMT1), dominantly inherited axonal neuropathies (CMT2) and recessively inherited neuropathies (CMT4). An investigation of these three groups is the focus of the INC, our RDCRC. Extensive progress in understanding the pathogenesis of inherited neuropathies has occurred but there are still no effective treatments for any form of CMT [3-5] and the first large scale therapeutic trials for CMT1A (the commonest form of CMT) are only now underway (Shy, Herrmann, Me Dermott and Reilly, members of the INC, are involved in these trials). Research into CMT is therefore at a critical point where the laboratory based basic science discoveries are beginning to be translated into treatments for patients (bench to bedside model). However, there remain major obstacles to the effective translation of these basic science discoveries into treatments including (1) the lack of widespread expertise in diagnosis and management of CMT, (2) the lack of accepted uniform methods of clinically analyzing different kinds of patients with CMT (including the lack of tools specifically designed for inherited neuropathy patients e.g. nerve imaging, disease biomarkers), (3), the lack of a disability or impairment scales to monitor children with CMT and the need to continually improve the current accepted CMT neuropathy score (CMTNS) [6] for monitoring adults, (4), the lack of natural history studies in most forms of CMT including CMT1B, CMT2A and CMT4A, (5), the lack of information of genetic modifiers of all forms of CMT, and finally, (6), the lack of trained inherited neuropathy trial physicians to conduct clinical trials in CMT. Among the most important of these needs is to specifically train neurologists interested in peripheral neuropathies for clinical research in inherited neuropathies. To date most neuromuscular fellowships are directed towards acquired neuropathies such as diabetes, inflammatory neuropathies and painful small fiber neuropathies as these are more common and have been more treatable to date. Although inherited neuropathies may be a small component of these fellowships we feel it is essential to specifically train neurologists to both understand the genetics, clinical presentation and physiology of the various forms of CMT and also to enable young investigators to conduct high level clinical research in the inherited neuropathies. Our ideal trainees would typically have completed a neuromuscular fellowship (or equivalent) and either be at advanced post-doctoral or junior faculty levels who wish to develop a clinical research career into inherited neuropathies. Senior specialist registrars (SPRs) in neurology would be at an equivalent developmental position in the UK. An ideal training program should be comprehensive and flexible (as outlined below) to train investigators in all forms of clinical research including research methods for clinical assessment and natural history studies (including clinical pattern recognition, neurophysiologic methodologies, neuromuscular imaging and nerve pathology), and the development expertise in clinical trial design and biostatistics. For select candidates, clinically related laboratory based research should also be possible

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
7U54NS065712-04
Application #
8478288
Study Section
Special Emphasis Panel (ZRG1-HOP-Y)
Project Start
Project End
Budget Start
2012-01-02
Budget End
2012-08-31
Support Year
4
Fiscal Year
2011
Total Cost
$95,311
Indirect Cost
Name
University of Iowa
Department
Type
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Horga, Alejandro; Laurà, Matilde; Jaunmuktane, Zane et al. (2017) Genetic and clinical characteristics of NEFL-related Charcot-Marie-Tooth disease. J Neurol Neurosurg Psychiatry 88:575-585
Tomaselli, Pedro J; Rossor, Alexander M; Horga, Alejandro et al. (2017) A de novo dominant mutation in KIF1A associated with axonal neuropathy, spasticity and autism spectrum disorder. J Peripher Nerv Syst 22:460-463
Bis, Dana M; Schüle, Rebecca; Reichbauer, Jennifer et al. (2017) Uniparental disomy determined by whole-exome sequencing in a spectrum of rare motoneuron diseases and ataxias. Mol Genet Genomic Med 5:280-286
Tomaselli, Pedro J; Rossor, Alexander M; Horga, Alejandro et al. (2017) Mutations in noncoding regions of GJB1 are a major cause of X-linked CMT. Neurology 88:1445-1453
Shy, Michael; Rebelo, Adriana P; Feely, Shawna Me et al. (2017) Mutations in BAG3 cause adult-onset Charcot-Marie-Tooth disease. J Neurol Neurosurg Psychiatry :
Panosyan, Francis B; Kirk, Callyn A; Marking, Devon et al. (2017) Carpal tunnel syndrome in inherited neuropathies: A retrospective survey. Muscle Nerve :
Ramdharry, Gita M; Pollard, Alexander J; Grant, Robert et al. (2017) A study of physical activity comparing people with Charcot-Marie-Tooth disease to normal control subjects. Disabil Rehabil 39:1753-1758
Rossor, Alexander M; Morrow, Jasper M; Polke, James M et al. (2017) Pilot phenotype and natural history study of hereditary neuropathies caused by mutations in the HSPB1 gene. Neuromuscul Disord 27:50-56
Liao, Chunyan; Ashley, Neil; Diot, Alan et al. (2017) Dysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutations. Neurology 88:131-142
Manganelli, Fiore; Parisi, Silvia; Nolano, Maria et al. (2017) Novel mutations in dystonin provide clues to the pathomechanisms of HSAN-VI. Neurology 88:2132-2140

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