Abstract

CMT affects 1/2500 people and there are no proven treatments that modify the disease. Clinical and basic research in inherited peripheral neuropathies is expanding rapidly on many fronts. Next generation sequencing enables the identification of novel genetic causes such that > 90 genes causing CMT neuropathy have now been identified, many by sites within the INC. Rational therapeutic approaches for the most common subtypes of CMT are being actively pursued or have even already developed. The INC needs to rapidly respond to new opportunities and needs that result from novel discoveries in fields such as genetic diagnosis, gene editing, cell biology, or outcome measures in CMT. To this end we propose a Pilot/Feasibility Core to support single- or multi-site projects that will advance the diagnosis, clinical trial readiness, management, and/or treatment of CMT subtypes. Approved projects will typically be approved for a single year, with a budget of $25,000 to $50,000. Funds will be available to support two Pilot/Feasibility projects per year. Junior INC investigators and senior investigators wishing to expand their research in new directions will be encouraged to apply. Evaluating Pilot/Feasibility applications and monitoring the projects will be the responsibility of the Pilot/Feasibility Core, which will be directed by Dr. Mario Saporta (the site-PI of the clinical University of Miami site and Dr. Alex Rossor (from our UCL site). They were the first two scholar/trainees of the INC 10 years ago, and are now recognized as independent investigators in our field. Core membership includes expertise in COAs, genetic diagnosis, and therapeutic development. Members include the INC leadership - Drs. Shy, Scherer, Herrmann, Reilly, Zchner, and Burns, as well as Drs. Finkel (an expert in neuromuscular trials) and Svaren (a member of our External Advisory Committee, and an expert in biomarker development) and representatives from two PAGS, Amy Gray (CMTA) and Dr. Amanda Haidet-Phillips (MDA).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54NS065712-13
Application #
10004179
Study Section
Special Emphasis Panel (ZTR1)
Project Start
2009-09-30
Project End
2024-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
13
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
University of Iowa
Department
Type
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242

  Publications

Saghira, Cima; Bis, Dana M; Stanek, David et al. (2018) Variant pathogenicity evaluation in the community-driven Inherited Neuropathy Variant Browser. Hum Mutat 39:635-642
Shy, Michael; Rebelo, Adriana P; Feely, Shawna Me et al. (2018) Mutations in BAG3 cause adult-onset Charcot-Marie-Tooth disease. J Neurol Neurosurg Psychiatry 89:313-315
Laurá, Matilde; Singh, Dishan; Ramdharry, Gita et al. (2018) Prevalence and orthopedic management of foot and ankle deformities in Charcot-Marie-Tooth disease. Muscle Nerve 57:255-259
Hu, Bo; McCollum, Megan; Ravi, Vignesh et al. (2018) Myelin abnormality in Charcot-Marie-Tooth type 4J recapitulates features of acquired demyelination. Ann Neurol 83:756-770
Dankwa, Lois; Richardson, Jessica; Motley, William W et al. (2018) A mutation in the heptad repeat 2 domain of MFN2 in a large CMT2A family. J Peripher Nerv Syst 23:36-39
Bai, Yunhong; Wu, Xingyao; Brennan, Kathryn M et al. (2018) Myelin protein zero mutations and the unfolded protein response in Charcot Marie Tooth disease type 1B. Ann Clin Transl Neurol 5:445-455
Rebelo, Adriana P; Saade, Dimah; Pereira, Claudia V et al. (2018) SCO2 mutations cause early-onset axonal Charcot-Marie-Tooth disease associated with cellular copper deficiency. Brain 141:662-672
Abbott, Jamie A; Meyer-Schuman, Rebecca; Lupo, Vincenzo et al. (2018) Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy. Hum Mutat 39:415-432
Abrams, Alexander J; Fontanesi, Flavia; Tan, Natalie B L et al. (2018) Insights into the genotype-phenotype correlation and molecular function of SLC25A46. Hum Mutat 39:1995-2007
Sandelius, Åsa; Zetterberg, Henrik; Blennow, Kaj et al. (2018) Plasma neurofilament light chain concentration in the inherited peripheral neuropathies. Neurology 90:e518-e524

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