Targeting microRNA-134 for seizure control and disease modification in epilepsy

EBioMedicine. 2019 Jul;45:646-654. doi: 10.1016/j.ebiom.2019.07.008. Epub 2019 Jul 9.


MicroRNA-134 is a brain-enriched small noncoding RNA that has been implicated in diverse neuronal functions, including regulating network excitability. Increased expression of microRNA-134 has been reported in several experimental epilepsy models and in resected brain tissue from temporal lobe epilepsy patients. Rodent studies have demonstrated that reducing microRNA-134 expression in the brain using antisense oligonucleotides can increase seizure thresholds and attenuate status epilepticus. Critically, inhibition of microRNA-134 after status epilepticus can potently reduce the occurrence of spontaneous recurrent seizures. Altered plasma levels of microRNA-134 have been reported in epilepsy patients, suggesting microRNA-134 may have diagnostic value as a biomarker. This review summarises findings on the cellular functions of microRNA-134, as well as the preclinical evidence supporting anti-seizure and disease-modifying effects of targeting microRNA-134 in epilepsy. Finally, we draw attention to unanswered questions and some of the challenges and opportunities involved in preclinical development of a microRNA-based oligonucleotide treatment for epilepsy.

Keywords: Biomarker; Epileptogenesis; Hippocampal sclerosis; Noncoding RNA; RNA therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Disease Models, Animal
  • Epilepsy / genetics
  • Epilepsy / pathology
  • Epilepsy / therapy*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / therapeutic use
  • Neurons / metabolism*
  • Neurons / pathology
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / therapeutic use
  • Seizures / genetics
  • Seizures / therapy*


  • MIRN134 microRNA, human
  • MicroRNAs
  • Oligonucleotides, Antisense