Targeting LDH enzymes with a stiripentol analog to treat epilepsy

Targeting metabolism to tackle seizures About 1% of us suffer from epilepsy. Unfortunately, presently available drugs do not work for a third of epileptic patients. Sada et al. wanted to develop compounds to treat drug-resistant epilepsy (see the Perspective by Scharfman). They focused 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. Searching for a substance that selectively targets this molecule, they found a potential anti-epileptic drug that strongly suppressed drug-resistant epilepsy in an animal model. Science , this issue p. 1362 ; see also p. 1312