癫痫 z-bo 2020-09-18 329

　　Mimicking a dietary manipulation sometimes used to treat epilepsy, researchers have discovered a drug that targets specific metabolic pathways in the brain and suppresses seizures in drug-resistant mouse epilepsy models. This approach, which departs from traditional treatment strategies that target neurons, may produce more effective anti-epileptic drugs; anti-epileptic drugs are currently only effective in about two-thirds of epilepsy patients. The ketogenic diet is a high-fat, low-carbon diet that was discovered in the 1920s to reduce drug-resistant seizures; it converts the main energy source of the brain from glucose to ketones; therefore, Nagisa Sada and colleagues were concerned about this change. What happens to the neuron is carefully observed. They focused on a metabolic pathway called astrocyte-neuronal lactate shuttle and discovered a molecule called lactate dehydrogenase (LDH), which seems to control brain excitability.

　　When the researchers inhibited LDH in a mouse model of epilepsy, they found that it hyperpolarized neurons and suppressed the seizures in these mice. The researchers then tested 20 anti-epileptic drugs and found that only one drug called stiripentol can inhibit LDH to some extent. They further discovered that stiripentol has a substructure called isosafrole; isosafrole itself seems to inhibit the production of lactic acid. In summary, their findings indicate that this class of stiripentol derivatives may provide better treatments for drug-resistant epilepsy.

　　A "Perspective" article by Helen Scharfman explains these results and their significance in more detail.