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Review
. 2016 Oct;29(5):537-48.
doi: 10.1097/WCO.0000000000000373.

Recent advances in the genetic neuropathies

Alexander M Rossor  1 , Pedro J Tomaselli, Mary M Reilly
Affiliations
Review

Recent advances in the genetic neuropathies

Alexander M Rossor et al. Curr Opin Neurol. 2016 Oct.

Abstract

Purpose of review: Charcot-Marie-Tooth disease (CMT) is one of the commonest inherited neuromuscular diseases with a population prevalence of 1 in 2500. This review will cover recent advances in the genetics and pathomechanisms of CMT and how these are leading to the development of rational therapies.

Recent findings: Pathomechanistic and therapeutic target advances in CMT include the identification of the ErbB receptor signalling pathway as a therapeutic target in CMT1A and pharmacological modification of the unfolded protein response in CMT1B. In CMT2D, due to mutations in glycyl-tRNA synthetase, vascular endothelial growth factor-mediated stimulation of the Nrp1 receptor has been identified as a therapeutic target. Preclinical advances have been accompanied by the publication of large natural history cohorts and the identification of a sensitive biomarker of disease (muscle MRI) that is able to detect disease progression in CMT1A over 1 year.

Summary: Advances in next-generation sequencing technology, cell biology and animal models of CMT are paving the way for rational treatments. The combination of robust natural history data and the identification of sensitive biomarkers mean that we are now entering an exciting therapeutic era in the field of the genetic neuropathies.

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Figures

Figure 1
Figure 1
This figure illustrates the genes involved in CMT. * Those genes for which clinical trials in man have either been performed or are in progress. ** Those genes for which there have been successful therapeutic trials in animal models of the disease.
See this image and copyright information in PMC

References

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