September 3, 2013
Image Caption: (Top Image) Zebrafish in the Baraban lab. (Bottom Image) Wild-type and larval zebrafish carrying a mutation in the SCN1A gene (mimicking a severe form of pediatric epilepsy) were used for drug screening. Credits: Dr. Baraban, UCSF
Brett Smith for redOrbit.com Your Universe Online
The phrase thinking outside the box has become so common these days, its almost thought of as an oxymoronic clich. However, a group of University of California, San Francisco researchers, doing just that, may have stumbled onto a new drug to treat a certain form of childhood epilepsy.
Although previous studies have found antihistamines can make seizures worse, the UCSF researchers found that the antihistamine clemizole can prevent seizures in zebrafish modified to replicate the rare form of childhood epilepsy called Dravet Syndrome.
This finding was completely unexpected. Based on what is currently known about clemizole, we did not predict that it would have antiepileptic effects, said study author Scott C. Baraban, a neurologist at UCSF.
Instead of expanding on previous drug research, Baraban and colleagues used a random test of 320 compounds that had already been approved for use by the Food and Drug Administration. The team said they could not tell which drugs were causing the observed results until after the individual tests had been completed.
In discussing the surprising beneficial effect of clemizole, the researchers said they had tried ten other antihistamines, including four tested in the study, and none showed an ability to block seizures. Baraban said that the antihistamine itself was most likely not the reason behind the drugs anti-seizure effect. He added that the group will be performing studies to try to figure out the actual mechanism.
Zebrafish used in the study were engineered to have a single mutation in the SCN1A gene that causes Dravet Syndrome. The fish were found to exhibit some of the same characteristics, including spontaneous seizures, typically seen in children with the condition, but not seen in normal, healthy zebrafish.
We were also surprised at how similar the mutant zebrafish drug profile was to that of Dravet patients, Baraban said. Antiepileptic drugs shown to have some benefits in patients (such as benzodiazepines or stiripentol) also exhibited some antiepileptic activity in these mutants. Conversely, many of the antiepileptic drugs that do not reduce seizures in these patients showed no effect in the mutant zebrafish.
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Researchers Use Zebrafish To Reel In New Epilepsy Treatment