“Fishing” for an Epilepsy Cure

Epilepsy, defined as a predisposition towards generating spontaneous, recurrent seizures, is a complex neurological disorder with a variety of causes and symptoms. One-third of people with epilepsy do not respond to current anti-epileptic therapy; and the people who do respond favorably to these medications can suffer from serious side-effects. Hence, there is an urgent need to better understand mechanisms that can cause seizures and epilepsy.

Scientists studying epilepsy use a variety of model organisms like rats, mice, and even sea-lions to understand what makes the brain capable of generating and sustaining spontaneous seizures. In recent years, researchers have started studying zebrafish in search of finding clues for better antiepileptic therapies. A tiny fish that is native to Southeast Asia, the zebrafish (Danio rerio) has been used as a tool for studying neurological disorders like Generalized axiety disorder, post-traumatic stress disorder and autism. These experiments have been conducted by Dr. Scott Baraban who is at the University of California, San Francisco (UCSF).

In epilepsy too, these fish are proving to be an indispensible and novel tool for the following reasons:

• They have enough homology (i.e., similarity) to humans, making it likely that what we find in the zebrafish may be of potential use in humans.
• Scientists have characterized the entire genome of the zebrafish; this is good news for epilepsy research because we can study epilepsies with a known genetic cause.
• It is relatively easy to carry out genetic and drug manipulations.
• Using zebrafish to investigate new drugs is a high throughput method, i.e., thousands of drugs can be tested in a relatively short period of time and with fewer resources than previously needed.
• It may seem like a long shot, but zebrafish can be used to study behavioral seizures as well. Although the seizures don’t look exactly similar to those that occur in people with epilepsy, zebrafish show behavior like erratic movements and hyperactivity that can be caught by special cameras.

While no experimental tool is perfect by itself, it is possible to envision a scenario where we first use medicinal chemistry to synthesize anti-epileptic drugs. Zebrafish can provide a fast and easy way to screen these drugs, and promising candidates can be studied in preclinical and ultimately clinical studies.