Infantile spasms (IS) is a rare and particularly severe epilepsy syndrome that typically begins within the first year of life. Infantile spasms is characterized by subtle seizures which can have large neurological effects and an atypical EEG pattern; these symptoms can lead to large developmental delays and cognitive and physical deterioration.
The exact mechanisms underlying infantile spasms are not completely understood.
Sadly, many primary care doctors and parents alike are not familiar with the signs and symptoms of infantile spasms. So, many children with infantile spasms do not receive treatment during the critical window within the weeks and months after the emergence of symptoms. Many other children do not respond to available treatments for infantile spasms or these treatments have substantial adverse side effects, giving these children a dire prognosis.
CURE EPILEPSY'S INFANTILE SPASMS RESEARCH INITIATIVE
With $4 million in funding, CURE Epilepsy launched the Infantile Spasms Initiative in 2013 as the first team science approach in the epilepsy research community. The initiative brought together eight researchers from different institutions to work as a team and study the pathology of infantile spasms. Collectively, the investigators studied the basic biology underlying IS, searched for biomarkers as well as novel drug targets, and developed improved treatments. Members of the multidisciplinary research team were:
- Chris Dulla, PhD – Tufts University
- Aristea Galanopoulou, MD, PhD – Albert Einstein College of Medicine
- Jeff Noebels, MD, PhD – Baylor College of Medicine
- John Swann, PhD – Baylor College of Medicine
- Libor Velisek, MD, PhD – New York Medical College
- Manisha Patel, PhD – University of Colorado Denver
- Doug Nordli, MD – Children’s Hospital of Los Angeles
- Elliott Sherr, MD, PhD – University of California, San Francisco
The CURE Epilepsy Infantile Spasms Initiative team published their findings in 2020. Key impacts from the Infantile Spasms Initiative include:
- Discovered a potential treatment and acquired a patent to reduce spasms and decrease side effects
- Identified the cell type and location where severe spasms start
- Revealed that brain activity prior to spasms resembles a sleep cycle phase
- Published 19 papers as a team to share new knowledge with other researchers in the field
- Secured 3 National Institute of Health grants as a team, with more than $4.4 million in total expected funding
Current Research for Infantile Spasms
Future Research for Infantile Spasms
INFANTILE SPASMS INITIATIVE IN ACTION
One of the CURE Epilepsy IS Initiative’s research groups, led by Dr. John Swann at the Baylor College of Medicine, focused its efforts on discovering novel drug targets and better treatment strategies to stop the spasms and the associated developmental delays.
The team identified that treatment with (1-3) IGF-1, a derivative of the growth hormone insulin-like growth factor 1 (IGF-1), reduced the spasms and irregular brain wave pattern in an animal model. Adding this compound to vigabatrin, an FDA-approved IS treatment, reduced the dose of vigabatrin required to eliminate the spasms. Diminishing the dosage also decreased the risk of serious side effects, including the potential for irreversible peripheral vision loss.
The Swann lab patented this combination treatment and used the discovery to obtain two National Institutes of Health (NIH) grants. One of these grants, totaling approximately $350,000 over five years, will investigate the molecular basis for the combination therapy. Through the second grant, the team will work to establish a specific IS rodent model for identifying more effective, less toxic therapies.
Through work partially funded by CURE Epilepsy’s IS Initiative, Dr. Swann’s team also identified the specific cell type and its location (the frontal lobe of the brain) where severe epileptic spasms often begin, revealing that brain activity immediately before epileptic spasms closely resembles a phase of the sleep cycle. These discoveries highlight potential avenues to prevent these spasms from occurring in future patients.