Scientists track down possible new treatment for epilepsy

Increasing the concentration of specific fats in the brain could suppress epileptic seizures. This is evident from new research carried out by the research groups of Professor Patrik Verstreken (VIB-KU Leuven) and Professor Wim Versées (VIB-Vrije Universiteit Brussel). The results of their close collaboration have been published in the journal Nature Structural & Molecular Biology.

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Verstreken specializes in brain research, focusing on synapses. In various brain disorders such as Parkinson's disease there is impaired communication at these synapses.

Versées examines the processes which take place in our cells, right down to the level of individual molecules and atoms. By figuring out the three-dimensional structures of protein molecules, he tries to obtain crucial information about their role in the cell and the mechanisms which underlie various disorders.

The key role of TBC1D24

In earlier research involving fruit flies, Verstreken had already demonstrated that a protein known as 'Skywalker' plays a crucial role in maintaining communication between brain cells. An almost identical protein operates in the human brain under the name 'TBC1D24'.

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Verstreken remarks: "Genetic mutations of the protein TBC1D24 cause a deviation known as the DOOR syndrome. Alongside deafness, deformed nails, brittle bones and mental retardation, this serious genetic disorder is characterized by neurodegeneration, movement disorders and epilepsy."

Analysis with atomic precision

By joining forces with Versées at the VIB research center for structural biology, the scientists were able to figure out the three-dimensional structure of Skywalker, making it possible to study the protein in microscopic detail.

"Looking at Skywalker in this way gave us completely new insights into the precise function of this protein, and therefore also the function of the human protein TBC1D24," notes Versées. "Among other things, we discovered that it connects with specific brain fats. And more importantly, this connection is impaired in over 70% of patients with a TBC1D24 mutation."

Suppression of epileptic seizures

On the basis of this discovery, the scientists increased the concentration of specific brain fats in fruit flies with a Skywalker mutation. What happened? The epileptic seizures in the sick fruit flies were completely suppressed.

"Our work shows that increasing specific brain fats at the synapses of patients with a TBC1D24 mutation is a possible strategy for preventing epileptic seizures. And although our work focuses on people with TBC1D24 mutations, we think that our findings could be relevant to various forms of epilepsy," says Verstreken.

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Scientific cross-pollination

"Our two research groups will now continue to collaborate in order to seek out strategies for increasing the concentration of specific fats in the brain to prevent epileptic seizures," Versées concludes. "This research stems from cross-pollination between structural biology, biochemistry and genetics, so we will certainly continue down this interdisciplinary route."

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VIB - Flanders Interuniversity Institute for Biotechnology   press release

Publication

Fischer B et al. Skywalker-TBC1D24 has a lipid-binding pocket mutated in epilepsy and required for synaptic function.  Nature Structural & Molecular Biology, Published Online September 26 2016. doi: 10.1038/nsmb.3297