An immuno- and growth-suppressant drug used to prevent rejection in human organ transplants and to treat some forms of cancer has proven effective in suppressing seizures in mice when used intermittently.
These findings, which appear in a recent edition of Epilepsia, could one day lead to a new approach in treating humans with some forms of epilepsy, say researchers at Baylor College of Medicine.
"The findings are significant. We showed intermittent rapamycin treatment, as opposed to continuous treatment, suppressed seizures in a genetic model of epilepsy that mimics a form of human epilepsy," said Dr. Joaquin Lugo, currently an assistant professor in the Department of Psychology and Neuroscience in Baylor University's College of Arts & Sciences in Waco, who contributed to this research while at BCM.
"Long-term, continuous treatment with rapamycin can lead to growth retardation, however, there were no adverse effects on growth following intermittent rapamycin treatment in the mice."
The study was conducted in the laboratory of Dr. Anne Anderson, associate professor of pediatric - neurology at BCM and a principal investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. Researchers there used mice genetically engineered to have hyperactivity of mammalian target of rapamycin (mTOR) signaling, which is the specific biochemical pathway targeted by the drug, rapamycin. It is also a pathway that has impaired regulation in some forms of human epilepsy.
Researchers studied the effects of administering the treatments for different periods of time. They found that the most effective outcome was two weeks with medication followed by three weeks without.
"Besides suppressing seizures, rapamycin also increased the engineered mice's longevity," Lugo said. "Whether the longer life is a result of fewer seizures, we don't know."
Lugo said he plans to do further lab research with rapamycin at Baylor University to explore possible links between autism and epilepsy.
"With both conditions the pathway mTOR, which plays an important role in the nervous system, is unusually active," he said.
Looking at long-term effects
The findings with animal models may indicate that lifelong treatment with the drug might not be necessary, although more research is needed to determine the long-term effects on humans, Lugo said.
Anderson added that these findings, "open to door to clinical trials - a rapid translation from bench to bedside. They also highlight the importance of translational research. The NRI, where the studies took place, was set up to facilitate this type of rapid translation of basic science research into treatment of children with devastating neurological disorders such as severe epilepsy and cognitive disorders."
Other researchers who contributed to this study include: C. Nicole Sunnen and Amy L. Brewster, both with The Cain Foundation Laboratories, the NRI and the Department of Neuroscience at BCM; Fabiola Vanegas, Eric Turcios and Shivani Mukhi, all with the Cain Foundation Laboratories, the NRI and the Department of Pediatrics at BCM; Deena Parghi, the Department of Pathology at BCM; and Gabriella D'Arcangelo, Department of Cell Biology and Neuroscience at Rutgers, The State University of New Jersey. The NRI is under the direction of Dr. Huda Zoghbi, professor of molecular and human genetics, pediatrics, neurology, and neuroscience at BCM.
The research was funded by the Epilepsy Foundation, Citizens United for Research in Epilepsy, The Vivian Smith Foundation, and the National Institutes of Health/National Institute for Neurological Disorders and Stroke with no conflict of interest by researchers.