Although any treatments built on these findings would be
decades away if they arrive at all, the genes in question feed into relatively
discrete, specialised biological pathways which are often more promising as
viable drug targets.
'More than a third of epilepsy patients are not treatable
with any medication, so the idea of finding specific drug targets, instead of a
drug that just bathes the brain and may cause problems with normal brain
function, is very appealing', said Professor Daniel Lowenstein of the
University of California, San Francisco, the co-leader of the Epi4k project
that led to the research.
The study, published in Nature, focused on two forms of severe childhood epilepsy, Lennox-Gastaut Syndrome and infantile spasms, where patients often have other
neurological conditions like autism or cognitive disability.
The scientists were particularly interested in the influence
of de novo gene mutations — where the central genetic defect is not inherited
from either patient but occurs spontaneously in the womb — and compared the DNA
of the 264 children selected with that of their parents.
As well as confirming genes that were already associated
with severe childhood epilepsy, the research two genes for the first time. One
of the genes, GABRB3, is involved in the rare neurological disorder Angelman
Syndrome, which raises the question of whether therapy for Angelman's patients
might be of benefit.
The other gene, ALG13, is involved in putting sugar on
proteins, which, the researchers say 'points to a new way of thinking about the
causes of and treatment for epilepsy'.
Professor Lowenstein said that of the gene mutations
identified or confirmed, 'many affect molecules that are involved in a
relatively limited number of cellular pathways. This suggests that it may be
sufficient to target therapies at a limited set of pathways rather than every
mutated protein in every patient'.
Speaking to GEN News, Dr Katrina Gwinn of the National
Institute of Neurological Disorders and Stroke in the USA, who was not involved
in the study, said the pathways research was a 'tremendously interesting part of
this paper. The study used an unbiased approach to identify and confirm
biological pathways that may be involved in severe forms of epilepsy. These
pathways may contain new therapeutic targets that have yet to be tested'.