Editors' ChoiceNeuroscience

Targeting metabolism to tackle seizures

Sci. Signal.  24 Mar 2015:
Vol. 8, Issue 369, pp. ec73
DOI: 10.1126/scisignal.aab1610

The presently available drugs do not work for a third of epileptic patients. Sada et al. sought to develop compounds to treat drug-resistant epilepsy (see the Perspective by Scharfman). By focusing on a metabolic pathway in the brain, the astrocyte-neuron lactate shuttle, they found that lactate dehydrogenase, a key molecule in nerve cell metabolism, controls brain excitability. By searching for a substance that selectively targeted this enzyme, they found a potential anti-epileptic drug that suppressed drug-resistant epilepsy in an animal model.

N. Sada, S. Lee, T. Katsu, T. Otsuki, T. Inoue, Targeting LDH enzymes with a stiripentol analog to treat epilepsy. Science 347, 1362–1367 (2015). [Abstract] [Full Text]

H. E. Scharfman, Metabolic control of epilepsy. Science 347, 1312–1313 (2015). [Abstract] [Full Text]