New Class of Drugs May Prevent Temporal Lobe Epilepsy

Epilepsy, a set of neurological disorders characterized by attacks involving motor or sensory malfunction with or without unconsciousness or involuntary muscle contraction, is the fourth most common neurological condition. One of the most common and challenging forms of epilepsy is temporal lobe epilepsy, which affects the parts of the brain which control memory and mood. During a temporal lobe seizure, a person may be unaware of what is occurring; they might look awake but be unable to respond. Their lips and hands may make repetitive movements. For some patients, there can be a devastating blend of emotions, thoughts and experiences. In some cases, old memories can recur; at other times, patients can have hallucinations. These symptoms are often called an ‘aura’ or a warning that an attack is about to occur. A temporal lobe seizure can vary in intensity from barely being perceptible, to causing fear and other unpleasant sensations. Epilepsy can seriously interfere with daily life, including obtaining a driver’s license, holding down a job or taking part in everyday activities.

Over time, repeated temporal lobe seizures can cause the hippocampus (which controls learning and memory) to shrink, leading to memory problems. The good news, however, is that scientists have discovered a potential new class of drugs that may prevent the development of temporal lobe epilepsy. The drugs have been discovered by researchers at Duke University during laboratory studies on mice. It is hoped that in the near future, these drugs can be used to stop the disease from interfering with learning processes and to reduce stress in those diagnosed with the disease.

Currently, there are medications available for patients with temporal lobe epilepsy, though they merely help curb symptoms. Additionally, current medications often produce a series of unwanted side effects, including weight gain, tiredness and dizziness. In some cases, surgery is performed to remove the temporal lobe and thereby put an end to seizures. Surgery, however, is not indicated for all patients. Not only is it risky; for many patients it does not produce the desired effect and it is not performed if seizures arise from more than one area in the brain or when the focus of the seizure cannot be identified. Up until now, no drugs have been found which could prevent or slow the progression of the disease.

The new compound has thus far not been tried on human subjects, though results have been promising on mice. Researchers stated that their hope was to be able to use this compound in the future, on patients who have had one episode of prolonged seizures. The drug would effectively stop these patients from becoming epileptic.

Sometimes, temporal lobe epilepsy arises after one episode of prolonged seizures, which can result from a number of causes in children. After an episode, a brain receptor known as TrkB becomes overactive, and could lead the patient to suffer from chronic epilepsy. However, the solution is not simply to block TrkB signaling, since the latter has many positive effects (for instance, this signaling prevents neurons from dying after a seizure). In their studies, the scientists at Duke University, led by James McNamara, M.D., discovered that the solution was to unlink one particular enzyme (phospholipase C (gamma) 1), from the TrkB receptor. Doing so was found to significantly reduce the number of seizures in mice.

The next step was to develop a protein-based drug (pY816), which prevents the TrkB receptor from linking with the harmful enzyme. When the drug was infused into the blood of mice for a period of three days following a prolonged seizure episode, the drug stopped the activation of the harmful enzyme, leading to lower frequency and intensity of seizures. Their findings suggest that studies on the TrkB receptor could be a viable new target for anti-epileptic drugs.

Currently, the team is working on more tests, in the hopes that the drug can be tested on human patients in the future. They are also studying the way in which the phospholipase C (gamma) 1 enzyme converts a normally working brain, into an epileptic one. Their study, entitled A Peptide Uncoupling BDNF Receptor TrkB from Phospholipase Cγ1 Prevents Epilepsy Induced by Status Epilepticus, was published in volume 88 (issue 3) of the journal, Neuron.

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