How One Little Fish with Big Potential Redefined Epilepsy Drug Research
More than 20 years ago, Epygenix co-founder Scott C. Baraban, Ph.D. developed the first-ever zebrafish models at the University of California, San Francisco (UCSF). Designed specifically for genetic epilepsies, this unique zebrafish-based drug discovery platform uses gene editing to create zebrafish models that accurately replicate genetic epilepsies. Zebrafish research in the Baraban Laboratory at UCSF was supported by funding from the National Institutes of Health (NIH), Dravet Syndrome Foundation, CURE Epilepsy, Lennox-Gastaut Foundation, Bow Foundation and CDKL5 Foundation. Awarded the Basic Science Research Award from the American Epilepsy Society in 2016, Dr. Baraban's research program has set a new standard for how seizures and epilepsy are studied.
Over 80% of Human Genes Can be Found in Zebrafish
After two decades of rigorous research, zebrafish have become a prominent and promising model for studying neurological disorders, especially rare genetic epilepsies. Existing epilepsy drug discovery programs in rodents typically apply an external condition to induce seizures, which can cause high false negative and high false positive rates. This development path lacks high throughput, is extremely costly, and is labor intensive.
With zebrafish, loss-of-function single gene mutations that closely mimic human disease can be easily modeled, providing a phenotype-based screening system that accurately, efficiently, and systematically identifies the most promising drug candidates. The platform accurately identified eight FDA-approved "standard-of-care" antiepileptic drugs (AEDs) that are prescribed to patients with Dravet Syndrome (DS), as well as AEDs that had no effect and are contra-indicated in this population. Since Epygenix was founded in 2016, we have licensed three candidates and their corresponding analogs.
Why the Zebrafish Model Works
The zebrafish model mimics human epilepsy phenotypes and is pharmacologically validated against multiple anti-epilepsy drugs (AEDs). It is the only preclinical animal model of DS to successfully predict two FDA approved anti-seizure medications (fenfluramine and stiripentol) as effective.
Drug candidates can be refocused to leverage newly discovered mechanisms of action, previously approved molecules are screened through multiple layers of phenotype-based assays.
Zebrafish have a rapid life cycle enabling high through-put screening that enabled Epygenix to pinpoint the six lead compounds among thousands of candidates, proving the screening method encompasses resolute efficiency and accurate selectivity.
The platform can be expanded to most genetic epilepsies, which represent roughly 20% of the entire epilepsy population.
DISCLOSURE: THE ZEBRAFISH PLATFORM WAS DEVELOPED IN THE BARABAN LABORATORY AT THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO (UCSF). EPYGENIX HAS LICENSED SPECIFIC DRUG CANDIDATES AND INTELLECTUAL PROPERTY DISCOVERED BY THE AFOREMENTIONED PLATFORM AT UCSF.