ARISEN (Autoimmunity, Rasmussen’s, Inflammation & Status Epilepticus research Network)

About This Grant

PROJECT SUMMARY Sudden onset immune-mediated neurologic syndromes can result in devastating long-term morbidity and mortality in children and adults. These conditions include rare and poorly understood neuroinflammatory diseases, such as autoimmune encephalitis (AE), new onset refractory status epilepticus (NORSE), and Rasmussen syndrome. ARISEN (Autoimmunity, Rasmussen's, Inflammation & Status Epilepticus research Network) is the first U.S. based multi-center registry including these diseases, which are thought to be caused by the immune system attacking the brain and can cause high risk for death and long-term neurological problems. Clinical trials have been lacking in these diseases, and we do not know the natural history, long term outcomes or optimal treatments in these disorders. Moreover, the diagnosis can be delayed, which can be catastrophic for patient outcomes. The goal of ARISEN is to address roadblocks in developing novel therapeutics for rare neuroinflammatory conditions to lead to improved clinical trial readiness, treatments, and long-term outcomes, including patient and caregiver reported outcomes. These rare conditions require a multi-center clinical research approach to interrogate the natural history and immunopathogenesis. To study these diseases, ARISEN (Autoimmunity, Rasmussens, Inflammation & Status Epilepticus research Network) is a synergistic effort between two consortia: CONNECT (CONquering Inflammation and Epilepsies ConsorTium), the first multi-center prospective pediatric focused U.S.-based registry for AE and Rasmussen's, and the NORSE Institute which recruits children and adults. Our central hypothesis is that these syndromes result in long-term sequelae, including risk for refractory seizures and poor neuropsychological outcomes, that may be mitigated by an improved understanding of their pathogenesis and natural history (Project 1) and optimal outcome assessment measures, including patient and caregiver reported outcomes (Project 2). We will also search for. novel biomarkers to aid in earlier diagnosis, more timely therapeutic intervention, and inform clinical trials by improved characterization and targeted treatment of the underlying immune dysregulation (Project 3). This grant would allow for the collection of electroencephalograms, magnetic resonance imaging, and longitudinal biospecimens to be used for future studies. MPIs Drs. Gombolay and Murray will co-direct the administrative core. Dr. Gombolay has led the CONNECT AE registry for five years, and Dr. Murray has 22 years of experience as PI of large-scale federally-funded patient cohorts, including an encephalitis cohort. The ARISEN pilot core will fund proposals that will utilize ARISEN, develop new resources, and foster collaboration to tackle the unmet needs in these diseases. The Career Enhancement Core will train the next generation of scientists in these conditions by providing educational sessions, mentorship, access to the registry, and funding support. ARISEN's multidisciplinary team of clinical experts and patient advocacy groups will begin to address the critical obstacles to future clinical trials, including improving treatments and outcomes for these patients and their caregivers.