Murine therapeutic models for Charcot-Marie-Tooth (CMT) disease

Br Med Bull. 2012 Jun:102:89-113. doi: 10.1093/bmb/lds010. Epub 2012 May 2.


Introduction or background: Charcot-Marie-Tooth (CMT) disease represents a broad group of inherited motor and sensory neuropathies which can originate from various genetic aberrations, e.g. mutations, deletions and duplications.

Sources of data: We performed a literature review on murine animal models of CMT disease with regard to experimental therapeutic approaches. Hereby, we focussed on the demyelinating subforms of CMT (CMT1). PubMed items were CMT, animal model, demyelination and therapy.

Areas of agreement: Patients affected by CMT suffer from slowly progressive, distally pronounced muscle atrophy caused by an axonal loss. The disease severity is highly variable and impairments may result in wheelchair boundness. No therapy is available yet.

Areas of controversy: Numerous rodent models for the various CMT subtypes are available today. The selection of the correct animal model for the specific CMT subtype provides an important prerequisite for the successful translation of experimental findings in patients.

Growing points: Despite more than 20 years of remarkable progress in CMT research, the disease is still left untreatable. There is a growing number of experimental therapeutic strategies that may be translated into future clinical trials in patients with CMT.

Areas timely for developing research: The slow disease progression and insensitive outcome measures hamper clinical therapy trials in CMT. Biomarkers may provide powerful tools to monitor therapeutic efficacy. Recently, we have shown that transcriptional profiling can be utilized to assess and predict the disease severity in a transgenic rat model and in affected humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Charcot-Marie-Tooth Disease / genetics
  • Charcot-Marie-Tooth Disease / therapy*
  • Disease Models, Animal*
  • Genetic Predisposition to Disease
  • Mice
  • Molecular Targeted Therapy / methods
  • Rats