somatic mutation contributes to intrinsic epileptogenicity in pediatric brain tumors

Drug repurposed to alleviate epileptic seizures

31 July 2019

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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References

1. Nature Medicine 24, 1662–1668 (2018). doi: 10.1038/s41591-018-0172-x