New treatment strategy for epilepsy

December 08, 2014

Researchers found out that the conformational defect in a specific protein causes Autosomal Dominant Lateral Temporal Lobe Epilepsy (ADLTE) which is a form of familial epilepsy. They showed that treatment with chemical corrector called "chemical chaperone" ameliorates increased seizure susceptibility in a mouse model of human epilepsy by correcting the conformational defect. This was published in Nature Medicine (December 8, 2014 electronic edition).

Mutations in the gene LGI1, encoding a secreted protein, cause familial temporal lobe epilepsy. The research group of Professor Masaki Fukata, Associate Professor Yuko Fukata, and Assistant Professor Norihiko Yokoi of the National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences (NINS), in collaboration with the group of Professor Masahiko Watanabe of the Hokkaido University Graduate School of Medicine, Professor Dies Meijer of the Erasmus University Medical Center in the Netherlands, and Professor Takao Hamakubo of the Research Center for Advanced Science and Technology, The University of Tokyo, investigated 22 mutations in the LGI1 gene found in patients with human epilepsy. In 19 mutations, LGI1 mutant protein was secretion-defective. One of these mutations was introduced to mice which produced symptoms of epilepsy. In LGI1 mutant mice, there was a decrease in the amount of LGI1 functioning normally outside the cell (i.e., synapse) due to the degradation by an intrinsic quality control system that rapidly degrades and eliminates mutant proteins.

A small molecule called chemical chaperone (4-phenylbutyrate) was administrated to LGI1 mutant mice with a view to correct the misfolding of the LGI1 mutant protein and to cause normal secretion to the synapse. It was found that the mice had decreased seizure susceptibility.

Epilepsy is a common brain disorder that affects 1% of the population. In some cases, current antiepileptic drugs have a limited role in the treatment. According to Professor Masaki Fukata, "Chemical chaperone treatment focused on correcting the misfolding in proteins has been tried in inherited diseases including cystic fibrosis and lysosome disease. This is the first for chemical chaperones to be applied as a therapeutic option for epilepsy. The same therapeutic strategy may also be of benefit to epilepsy caused by genetic mutations other than LGI1 gene. We propose a novel therapeutic strategy for epilepsy."

National Institutes of Natural Sciences

Related Epilepsy Articles from Brightsurf:

Focal epilepsy often overlooked
Having subtler symptoms, a form of epilepsy that affects only one part of the brain often goes undiagnosed long enough to cause unexpected seizures that contribute to car crashes, a new study finds.

Antibodies in the brain trigger epilepsy
Certain forms of epilepsy are accompanied by inflammation of important brain regions.

Breaching the brain's defense causes epilepsy
Epileptic seizures can happen to anyone. But how do they occur and what initiates such a rapid response?

Using connectomics to understand epilepsy
Abnormalities in structural brain networks and how brain regions communicate may underlie a variety of disorders, including epilepsy, which is one focus of a two-part Special Issue on the Brain Connectome in Brain Connectivity, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers.

Epilepsy: Triangular relationship in the brain
When an epileptic seizure occurs in the brain, the nerve cells lose their usual pattern and fire in a very fast rhythm.

How concussions may lead to epilepsy
Researchers have identified a cellular response to repeated concussions that may contribute to seizures in mice like those observed following traumatic brain injury in humans.

Understanding epilepsy in pediatric tumors
A KAIST research team led by Professor Jeong Ho Lee of the Graduate School of Medical Science and Engineering has recently identified a neuronal BRAF somatic mutation that causes intrinsic epileptogenicity in pediatric brain tumors.

Can medical marijuana help treat intractable epilepsy?
A new British Journal of Clinical Pharmacology review examines the potential of medicinal cannabis -- or medical marijuana -- for helping patients with intractable epilepsy, in which seizures fail to come under control with standard anticonvulsant treatment.

Fertility rates no different for women with epilepsy
'Myth-busting' study among women with no history of infertility finds that those with epilepsy are just as likely to become pregnant as those without.

Do women with epilepsy have similar likelihood of pregnancy?
Women with epilepsy without a history of infertility or related disorders who wanted to become pregnant were about as likely as their peers without epilepsy to become pregnant.

Read More: Epilepsy News and Epilepsy Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to