Tuberous Sclerosis: A New Frontier in Targeted Treatment of Autism

Neurotherapeutics. 2015 Jul;12(3):572-83. doi: 10.1007/s13311-015-0359-5.


Tuberous sclerosis complex (TSC) is a genetic disorder with a high prevalence of autism spectrum disorder (ASD). Tremendous progress in understanding the pathogenesis of TSC has been made in recent years, along with initial trials of medical treatment aimed specifically at the underlying mechanism of the disorder. At the cellular level, loss of TSC1 or TSC2 results in upregulation of the mechanistic target of rapamycin (mTOR) pathway. At the circuitry level, TSC and mTOR play crucial roles in axonal, dendritic, and synaptic development and function. In this review, we discuss the molecular mechanism underlying TSC, and how this disease results in aberrant neural connectivity at multiple levels in the central nervous system, leading to ASD symptoms. We then review recent advances in mechanism-based treatments of TSC, and the promise that these treatments provide for future mechanism-based treatment of ASD. Because of these recent advances, TSC represents an ideal model for how to make progress in understanding and treating the mechanisms that underlie ASD in general.

Publication types

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

MeSH terms

  • Animals
  • Autism Spectrum Disorder / complications*
  • Autism Spectrum Disorder / drug therapy*
  • Autism Spectrum Disorder / metabolism
  • Brain / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Epilepsy / complications
  • GABA Agents / therapeutic use
  • Humans
  • Neurons / metabolism
  • Neurons / pathology
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / metabolism
  • Tuberous Sclerosis / complications*
  • Tuberous Sclerosis / drug therapy*
  • Tuberous Sclerosis / metabolism
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins / metabolism
  • Vigabatrin / therapeutic use


  • GABA Agents
  • TSC1 protein, human
  • TSC2 protein, human
  • Tuberous Sclerosis Complex 1 Protein
  • Tuberous Sclerosis Complex 2 Protein
  • Tumor Suppressor Proteins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Vigabatrin