PURPOSE OF REVIEW:
Charcot-Marie-Tooth disease (CMT) and related neuropathies represent a heterogeneous group of hereditary disorders. The present review will discuss the most recent advances in the field.
Knowledge of CMT epidemiology and frequency of the main associated genes is increasing, with an overall prevalence estimated at 10-28/100 000. In the last years, the huge number of newly uncovered genes, thanks to next-generation sequencing techniques, is challenging the current classification of CMT. During the last 18 months other genes have been associated with CMT, such as PMP2, MORC2, NEFH, MME, and DGAT2. For the most common forms of CMT, numerous promising compounds are under study in cellular and animal models, mainly targeting either the protein degradation pathway or the protein overexpression. Consequently, efforts are devoted to develop responsive outcome measures and biomarkers for this overall slowly progressive disorder, with quantitative muscle MRI resulting the most sensitive-to-change measure.
This is a rapidly evolving field where better understanding of pathophysiology is paving the way to develop potentially effective treatments, part of which will soon be tested in patients. Intense research is currently devoted to prepare clinical trials and develop responsive outcome measures.