24-03-2015 | Targeting Brain Metabolism Could Offer New Way to Treat Epilepsy

24 March 2015
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Researchers in Japan are exploring "a novel" new way to treat epilepsy involving inhibiting a metabolic pathway in neuron-helper cells.

It is hoped that this new treatment, which has proven to supress seizures in mice, will help those with difficult to control epilepsy.

About one third of people with epilepsy do not respond to anti-epileptic drugs despite numerous different combinations being tried.

Detlev Boison, the director of neurobiology at Legacy Research Institute in Portland, Oregon, although not involved in the study has stated - "This is a major discovery that will revolutionize the field, this study shows that there are other ways to look at treating epilepsy."

The target is the enzyme lactate dehydrogenase (LDH). It plays a role in how brain cells generate energy from glucose. In one part of the process, astrocytes use enzymes, including LDH, to turn glucose into lactate, which they then shuttle to neurons. The nerve cells convert lactate to pyruvate, which enters the citric acid cycle, a major metabolic pathway that produces chemical energy for the cell.

Tsuyoshi Inoue of Okayama University and colleagues focused on inhibiting LDH because some epilepsy patients find relief from seizures when they switch to a low-carbohydrate, high-fat diet that makes brain cells skip the LDH-driven astrocyte process. This ketogenic diet forces the brain to switch from burning glucose to burning fat metabolites called ketone bodies, which get pushed directly into the citric acid cycle.

The researchers found that blocking LDH directly mimics the ketogenic diet's effects (Science 2015, DOI: 10.1126/science.aaa1299). When they injected an LDH inhibitor into the hippocampus of mice with epilepsy-like symptoms, they observed fewer high-voltage spikes, a cellular sign of seizures, than seen in mice receiving a saline injection.

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