Topiramate for treatment of neonatal seizures and periventricular leukomalacia
Inventors: Frances Jensen, Pamela Follett, Joseph Volpe, Paul Rosenberg
Invention Types: Therapeutics
Research Areas: Neurology/Neuroscience
Keywords: Disease Model, New Indication/Use, Small Molecule/DrugFor More Information Contact: Caron, Connie
Topiramate, an AMPA glutamate receptor blocker, is FDA-approved to control seizures in adults and children over age 3. Dr. Jensen and colleagues showed that it prevented further brain damage in rats with periventricular leukomalacia (PVL) -like injury, a condition in premature babies that is the main antecedent to cerebral palsy. They also found that newborn rats with seizures caused by oxygen deprivation, the most common cause of seizures in term infants, were less susceptible to further seizures if they were treated with topiramate after injury occurred.
Topiramate may help prevent epilepsy in children who have seizures as newborns and may protect preterm newborns against PVL. Around 80,000 babies in the US are affected by seizures each year. Seizures in newborns can result in lifelong complications: 15-30% will develop epilepsy by age 7. About 55,000 babies are born premature and this number is rising due to improved medical techniques. Preterm infants are vulnerable to complications that can lead to PVL. 10-15% of patients with PVL will be affected with cerebral palsy.
No drug has been developed to date to block neonatal seizures, and there is currently no treatment or cure for PVL. Due to the inherent differences between adult and newborn brains, standard antiseizure and anticonvulsant medications are inadequate, ineffective and toxic to infants who experience seizures. Topiramate targets a receptor specifically overexpressed in preterm and neonatal brains, and it is able to prevent additional brain injury after the insult has occurred. Moreover, topiramate has a well known safety profile due to its market experience. Taken together, evidence from Dr. Jensen's work indicates that topiramate may be effective as a treatment for neonatal seizures and for PVL.
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Key Publications: US patent number: 6,921,775
J Neurosci. 2004 May 5;24(18):4412-20;| Epilepsia. 2004 Jun;45(6):569-75