somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors

Journal: Nature Medicine

Published: 2018-09-17

DOI: 10.1038/s41591-018-0172-x

Affiliations: 17

Authors: 18

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Research Highlight

Drug repurposed to alleviate epileptic seizures

© haydenbird/Getty

© haydenbird/Getty

A drug commonly used to treat skin cancer could help reduce the frequency of seizures in children with brain tumours and uncontrolled epilepsy.

A KAIST-led team reanalysed DNA sequencing data from 56 brain tumours in children; in half the patients, they identified activating mutations in a gene called BRAF.

Gene expression profiling on three BRAF-mutant brain samples showed that elevated expression of a regulatory gene called REST led to lower activity of other genes involved in healthy brain development and function.

Using mouse models, the researchers demonstrated that mutant BRAF expression influences the development of different types of brain cells in different ways, leading to the promotion of seizures as well as brain tumours.

Notably, a BRAF-targeted drug that is marketed for treating melanoma alleviated seizures in the mice, as did genetic inhibition of REST. The findings thus reveal two new potential drug targets for intractable epilepsy, one of which involves an already approved agent.

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  1. Nature Medicine 24, 1662–1668 (2018). doi: 10.1038/s41591-018-0172-x
Institutions Share
KAIST Graduate School of Medical Science and Engineering, South Korea 0.16
KAIST Department of Biological Sciences, South Korea 0.14
KAIST School of Electrical Engineering (EE), South Korea 0.11
KAIST BioMedical Science and Engineering Interdisciplinary Program (BSEIP), South Korea 0.10
KAIST Department of Bio and Brain Engineering, South Korea 0.08
Center for Cognition and Sociality (CCS), IBS, South Korea 0.08
Department of Pathology, Yonsei University, South Korea 0.06
Yonsei Institute of Pharmaceutical Sciences (YIPS), Yonsei University, South Korea 0.06
College of Medicine, CNU, South Korea 0.06
Severance Children's Hospital, Yonsei University, South Korea 0.04
KAIST Program of Brain and Cognitive Engineering, South Korea 0.03
Department of Pediatrics, Yonsei University, South Korea 0.02
Epilepsy Research Institute, Yonsei University, South Korea 0.02
Department of Neurosurgery, Yonsei University, South Korea 0.02
Brain Korea 21 Project for Medical Science, Yonsei University, South Korea 0.02
Center for Synaptic Brain Dysfunctions, IBS, South Korea 0.02