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Brief Description:

Using a rodent model of epilepsy, researchers found one of the body's own neurotransmitters released during seizures turns on a signaling pathway in the brain that increases production of a protein that could reduce medication entry into the brain.

Transcript:

Akinso: A brain study may lead to improved epilepsy treatments.

Miller: We're interested in increasing the efficacy of central nervous system acting drugs in epilepsy.

Akinso: Dr. David Miller is the Principal Investigator in the Laboratory of Pharmacology at the National Institute of Environmental Health Sciences. He explains that there are two problems with epilepsy drugs:

Miller: One is variable responses by patients to these drugs. So physicians will often have to change drugs in the course of therapy and second problem is 30 percent of epileptics don't respond to any of the drugs and that makes it very difficult.

Akinso: Because the drugs only work sometimes with some people, Dr. Miller asked the question-what is it about the way the brain works?

Miller: And one of the theories that have been in the literature for a long time is that it's the blood brain barrier preventing these drugs from getting from the blood into the central nervous system.

Akinso: The blood-brain barrier, which resides in brain capillaries, is a limiting factor in treatment of many central nervous system disorders. It is altered in epilepsy so that it no longer permits free passage of administered antiepileptic drugs into the brain. Using a rodent model of epilepsy, researchers found one of the body's own neurotransmitters released during seizures turns on a signaling pathway in the brain that increases production of a protein that could reduce medication entry into the brain. Dr. Miller said their work identifies the way seizures increase production of a drug-transport protein in the blood brain barrier.

Miller: Within the blood-brain barrier, there are these transporters, the major one being P-glycoprotein and they basically kick drugs back into the circulation and don't permit them to get into the central nervous system. So the hypothesis we tested was that if you could manipulate P-glycoprotein expression in the blood-brain barrier you could improve pharmacal therapy for epilepsy patients.

Akinso: Dr. Miller said targeting blood-brain barrier signals that increase P-glycoprotein expression suggests a promising way to improve the effectiveness of drugs that are used to treat epilepsy, though more research is needed before new therapies can be developed.

Miller: This is a new way of looking at pharmacal therapy. What we're doing basically is using the blood-brain barrier's own signaling system to repress changes that make it harder for the drugs to get in. In essence what we have is some sort of combination therapy we're proposing. One that hits the signaling system and the second one that goes into the brain after the signaling system is hit and gets into the targets in the neurons, which is where the antiepileptic drugs are working.

Akinso: He added that these findings provide insight into one mechanism that underlies drug resistance in epilepsy and possibly other central nervous system disorders. This is Wally Akinso at the National Institutes of Health, Bethesda, Maryland.