Clinical Center for the Lafora Epilepsy Cure Initiative (LECI): Clinical Trial Readiness for a Global Curative Drug Trial (P4.245)

Objective: Our objective is to report the advances of the Lafora Epilepsy Cure Initiative (LECI) Clinical Center, whose mission is to cure Lafora Disease (LD). Background: There is no cure for LD, an invariably fatal epilepsy syndrome. The hope for a cure began with the discovery of mutations responsible for the majority of LD cases in the 1990s and independent laboratories labored towards this goal for the next two decades. In 2014, the world’s leading LD researchers were brought together by Chelsea’s Hope, a parent-run group, to discuss ways to collaborate and accelerate drug development. LECI was born and various molecules may be ready for trials in as little as 2–5 years. The LECI Clinical Center was created to ensure clinical trial readiness for an imminent curative drug trial. Design/Methods: Clinicians/researchers who reported on or had experience with LD were invited to join the Clinical Center. Three international workshops were held and focus groups were used to develop a multi-year study plan that will identify, enroll, and register all patients with LD and promote clinical trial readiness. Results: The Clinical Center now encompasses 15 sites globally. The study plan developed includes initial natural history (NH) studies that will collect detailed phenotypic/genotypic information to inform outcome measures. An LD Progression scale incorporating 4 domains identified to be indicative of disease progression (epilepsy, cognition, ataxia, QOL/function) was developed as a primary outcome measure and is ready for validation. Potential biomarkers were identified and experts were recruited to lead biomarker study including: voxel-based morphometry, electrophysiology, and glucan phosphatase activity. Protocols and study instruments for an initial retrospective NH study have been finalized. Conclusions: Curative/disease-modifying LD drug trials are imminent. An extensive study plan has been developed and LECI is poised to take the first steps towards clinical trial readiness with a retrospective NH study beginning April 2017. Study Supported by: The Lafora Epilepsy Cure Initiative is supported by a NINDS Program Project Grant (P01-NS097197-01) awarded to M. Gentry, J. Serratosa, B. Minassian listed above along with P. Roach, J. Guinovart, A. De-Paoli Roach. Disclosure: Dr. Nguyen has nothing to disclose. Dr. Duron has nothing to disclose. Dr. Michelucci has nothing to disclose. Dr. Genton has nothing to disclose. Dr. Sinha has nothing to disclose. Dr. Beydoun has nothing to disclose. Dr. Arabi has nothing to disclose. Dr. Kecmanovic has nothing to disclose. Dr. Whitehouse has nothing to disclose. Dr. Keselman has nothing to disclose. Dr. Martinez-Juarez has received personal compensation for activities with Abbott Laboratories, Inc. Dr. Guilhoto has nothing to disclose. Dr. Salas-Puig has nothing to disclose. Dr. Bailey has nothing to disclose. Dr. Ben-Menachem has received personal compensation for activities with Bial, Eisai, UCB Pharma, and Abbott as a consultant and/or advisory board member. Dr. Ben-Menachem has received research support from Bial, Eisai, and UCB Pharma. Dr. Gentry has nothing to disclose. Dr. Minassian has nothing to disclose. Dr Serratosa has received personal compensation for activities with UCB, Esteve, Eisai Ltd, Bial, and Cyberonics. Dr. Delgado-Escueta has nothing to disclose.