Using zebrafish, UCSF screened 3,500 potential drug treatments for a single genetic epilepsy disorder in less than five years at a cost of less than $5 million. Normally this would take 15 years and $800 million.
Piper Wood had her first seizure when she was 6 months old – on a family vacation, in a setting meant for sunscreen and snorkels. Her diagnosis: Dravet syndrome, a catastrophic form of epilepsy marked by fierce seizures – sometimes hundreds in the course of a day – that eventually lead to cognitive and social impairment.
“An epilepsy diagnosis is very difficult to deliver to a family because the sheer nature of seizures is just so unpredictable,” says Joseph Sullivan, MD (above, right), Piper’s neurologist and director of the Pediatric Epilepsy Center of Excellence at UCSF Benioff Children’s Hospitals. “About one-third of our pediatric epilepsy patients continue to have seizures, even with optimal treatment.”
Piper’s father, Tim Wood, worked with Sullivan to initiate research that upended the field. Sullivan and his colleagues proved that Dravet is twice as prevalent as previously estimated, a finding that has helped other kids with this devastating disease. Wood is one of a number of parents of children with epilepsy who have partnered with physicians and scientists at UCSF to reimagine an entirely new care-delivery and drug-discovery model.
The lab of Scott Baraban, PhD (above, left), generates genetically engineered zebrafish models for Dravet and the more than 70 other genetically caused types of childhood epilepsy.
Unlike mice, which may produce only one or two pups per litter with the mutation, adult zebrafish can give birth within a week to more than 100 larvae with the same mutation, enabling Baraban’s lab to screen up to 100 drugs per month. For perspective, the National Institutes of Health funds an epilepsy drug program that screens about 200 drugs per year at a cost of approximately $4 million.
“In less than five years, we have screened more than 3,500 drugs using this Dravet fish,” Baraban says. “We have discovered five promising drugs, and in some cases, because they were previously approved by the FDA, they are going straight from zebrafish to patients.”
That process – progressing a drug from animal model to patient – typically takes 15 years or more and can cost more than $800 million. The Baraban Lab has successfully identified new drugs for Dravet syndrome in less than five years and at a cost of less than $5 million. True to UCSF’s public mission, he is making these zebrafish models available to researchers everywhere so scientists the world over can work simultaneously to find cures for kids like Piper as fast as they possibly can.
Scott Baraban is the William K. Bowes Jr. Professor of Neuroscience Research.