GABA-ergic cell therapy for epilepsy: Advances, limitations and challenges. (March 2016)

• Record Type: Journal Article
• Authors: Shetty, Ashok K.; Upadhya, Dinesh
• Is Part Of: Neuroscience and biobehavioral reviews. Volume 62(2016)
• Page Start: 35
• Page End: 47
• Publication Date: 2016-03
• Subjects: Epilepsy -- GABA-ergic interneurons -- Lateral ganglionic eminence -- Medial ganglionic eminence -- Neural cell grafts -- Pain -- Schizophrenia -- Stem cell therapy -- Temporal lobe epilepsy; Psychophysiology -- Periodicals; Human behavior -- Periodicals; Animal behavior -- Periodicals; Neurology -- Periodicals; Behavior -- Periodicals; Ethology -- Periodicals; Neurology -- Periodicals; Psychophysiologie -- Périodiques; Comportement humain -- Périodiques; Animaux -- Mœurs et comportement -- Périodiques; Neurologie -- Périodiques; Animal behavior; Human behavior; Neurology; Psychophysiology; Periodicals; Electronic journals; 573.8
• DOI: 10.1016/j.neubiorev.2015.12.014
• Languages: English
• ISSNs: 0149-7634

Abstract

Highlights: Drug-resistant epilepsy is seen in a significant fraction of epilepsy patients. Cell therapy is one of the emerging strategies investigated rigorously in preclinical models of epilepsy. GABA-ergic progenitor cell grafts derived from multiple sources have ability to reduce seizures. Several issues need resolution for clinical translation of GABA-ergic cell therapy for epilepsy. 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.