NIH: “Bench-to-bedside” describes research that has progressed from basic science in animal models that has led to therapies used in patients. Now, a study in the journal Brain describes what could be considered a direct “aquarium-to-bedside” approach, taking a drug discovered in a genetic zebrafish model of epilepsy and testing it, with promising results, in a small number of children with the disease. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
“This is the first time that scientists have taken a potential
therapy discovered in a fish model directly into people in a clinical
trial,” said Vicky Whittemore, Ph.D., program director at the NINDS.
“These findings suggest that it may be possible to treat neurological
disorders caused by genetic mutations through an efficient and precision
Scott C. Baraban, Ph.D., the William K. Bowes Jr. Endowed Chair in
Neuroscience Research and professor of neurological surgery at the
University of California, San Francisco (UCSF), postdoctoral fellow
Aliesha Griffin, Ph.D., and colleagues used a zebrafish model of Dravet
syndrome to test the drug lorcaserin and found that it suppressed
seizure activity in the fish. Dravet syndrome is a severe form of
pediatric epilepsy characterized by frequent daily drug-resistant
seizures and developmental delays. It is caused by a genetic mutation,
which Dr. Baraban’s group was able to introduce into the zebrafish to
Dr. Baraban and his colleague Kelly Knupp, M.D. at the University of
Colorado, Denver, then tested lorcaserin in five children with Dravet
syndrome. The children were resistant to other anti-epileptic drugs and
participated in this study through a compassionate use, off-label
program. Lorcaserin was initially associated with decreased seizure
frequency in all of the children. For example, during the first three
months of treatment, one of the patients who had been experiencing
multiple seizures every day, became seizure-free for two weeks. After
three months, however, seizure activity had increased, but the frequency
was less than had been reported at the start of the trial. None of the
children experienced severe side effects, although some reported a
This builds on work from a 2013 study in which Dr. Baraban and his
team at UCSF used an automated drug screening method to identify
potential anti-epileptic therapies and discovered that the compound
clemizole decreased seizure activity in the zebrafish.
In the current study, Dr. Baraban’s team discovered that clemizole
may have its anti-seizure effects by acting on the serotonin system.
Serotonin is a brain chemical that plays a role in various functions,
including mood, appetite and memory. The researchers next identified a
comparable drug, lorcaserin, which also affects the serotonin system and
is available for clinical use.
“Using zebrafish, we can greatly reduce the time between
identification of a potential treatment and getting it to individuals
who desperately need help,” said Dr. Baraban.
Dr. Baraban’s group is currently developing clemizole and its
derivatives, for use in clinical trials. In addition, the researchers at
UCSF are conducting experiments to learn more about the role of
specific serotonin receptors in epilepsy in hopes of generating more
effective treatments for children suffering from Dravet syndrome.
This work was supported by the NINDS (NS079214).
Griffin A et al. Clemizole and modulators of serotonin signaling suppress seizures in Dravet syndrome. Brain. January 2017.
For more information: