Rett Syndrome: Reaching for Clinical Trials

Neurotherapeutics. 2015 Jul;12(3):631-40. doi: 10.1007/s13311-015-0353-y.


Rett syndrome (RTT) is a syndromic autism spectrum disorder caused by loss-of-function mutations in MECP2. The methyl CpG binding protein 2 binds methylcytosine and 5-hydroxymethycytosine at CpG sites in promoter regions of target genes, controlling their transcription by recruiting co-repressors and co-activators. Several preclinical studies in mouse models have identified rational molecular targets for drug therapies aimed at correcting the underlying neural dysfunction. These targeted therapies are increasingly translating into human clinical trials. In this review, we present an overview of RTT and describe the current state of preclinical studies in methyl CpG binding protein 2-based mouse models, as well as current clinical trials in individuals with RTT.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autism Spectrum Disorder / drug therapy*
  • Autism Spectrum Disorder / genetics*
  • Brain / metabolism
  • Brain / pathology
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Humans
  • Methyl-CpG-Binding Protein 2 / genetics
  • Mice
  • Mutation
  • Neurons / metabolism
  • Neurons / pathology
  • Rett Syndrome / drug therapy*
  • Rett Syndrome / genetics*


  • MECP2 protein, human
  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2