GABA-ergic cell therapy for epilepsy: Advances, limitations and challenges

Neurosci Biobehav Rev. 2016 Mar;62:35-47. doi: 10.1016/j.neubiorev.2015.12.014. Epub 2015 Dec 31.

Abstract

Diminution in the number of gamma-amino butyric acid positive (GABA-ergic) interneurons and their axon terminals, and/or alterations in functional inhibition are conspicuous brain alterations believed to contribute to the persistence of seizures in acquired epilepsies such as temporal lobe epilepsy. This has steered a perception that replacement of lost GABA-ergic interneurons would improve inhibitory synaptic neurotransmission in the epileptic brain region and thereby reduce the occurrence of seizures. Indeed, studies using animal prototypes have reported that grafting of GABA-ergic progenitors derived from multiple sources into epileptic regions can reduce seizures. This review deliberates recent advances, limitations and challenges concerning the development of GABA-ergic cell therapy for epilepsy. The efficacy and limitations of grafts of primary GABA-ergic progenitors from the embryonic lateral ganglionic eminence and medial ganglionic eminence (MGE), neural stem/progenitor cells expanded from MGE, and MGE-like progenitors generated from human pluripotent stem cells for alleviating seizures and co-morbidities of epilepsy are conferred. Additional studies required for possible clinical application of GABA-ergic cell therapy for epilepsy are also summarized.

Keywords: Epilepsy; GABA-ergic interneurons; Lateral ganglionic eminence; Medial ganglionic eminence; Neural cell grafts; Pain; Schizophrenia; Stem cell therapy; Temporal lobe epilepsy.

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
  • Cell Differentiation / physiology*
  • Epilepsy / physiopathology
  • Epilepsy / therapy*
  • Epilepsy, Temporal Lobe / therapy*
  • GABAergic Neurons / cytology*
  • Hippocampus / cytology
  • Humans
  • Neural Stem Cells / cytology*