Kahoud, Robert J.

Febrile infection‐related epilepsy syndrome (FIRES) is a devastating epileptic encephalopathy with limited treatment options and an unclear etiology. Anakinra is a recombinant version of the human interleukin‐1 receptor antagonist used to treat autoinflammatory disorders. This is the first report of anakinra for treatment of a child with super‐refractory status epilepticus secondary to FIRES. Anakinra was well tolerated and effective. Cerebral spinal fluid analysis revealed elevated levels of proinflammatory cytokines before treatment that normalized on anakinra, suggesting a potential pathogenic role for neuroinflammation in FIRES. Further studies are required to assess anakinra efficacy and dosing, and to further delineate disease etiology. Ann Neurol 2016;80:939–945

AbstractCNSregeneration is a desirable goal for diseases of brain and spinal cord. Current therapeutic strategies for the treatment of multiple sclerosis (MS) aim to eliminate detrimental effects of the immune system, so far without reversing disability or affecting long‐term prognosis in patients. Approachable molecular targets that stimulateCNSrepair are not part of the clinical praxis or have not been identified yet. The purpose of this study was to identify the molecular target of the human monoclonal antibodyHIgM12.HIgM12 reverses motor deficits in chronically demyelinated mice, a model ofMS. Here, we identified polysialic acid (PSA) attached to the neural cell adhesion molecule (NCAM) as the antigen forHIgM12 by using differentNCAMknockout strains and throughPSAremoval from theNCAMprotein core. Antibody binding toCNStissue and primary cells, antibody‐mediated cell adhesion, and neurite outgrowth onHIgM12‐coated nitrocellulose was detected only in the presence ofPSAas assessed by western blotting, immunoprecipitation, immunocytochemistry, and histochemistry. We conclude thatHIgM12 mediates it'sin vivoandin vitroeffects through binding toPSAand has the potential to be an effective therapy forMSand neurodegenerative diseases.imageThe human antibody HIgM12 stimulates neurite outgrowthin vitroand promotes function in chronically demyelinated mice, a model of multiple sclerosis. The cellular antigen for HIgM12 was undetermined. Here, we identified polysialic acid attached to NCAM (neural cell adhesion molecule) as the cellular target for HIgM12. This includes glial fibrillary acidic protein (GFAP)‐positive mouse astrocytes (GFAP, red; HIgM12, green; DAPI, blue) among other cell types of the central nervous system. These findings indicate a new strategy for the treatment of neuro‐motor disorders including multiple sclerosis.