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OBJECTIVE: Patients with myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro-axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON-independent retinal atrophy can be detected in MOGAD. METHODS: Eighty MOGAD patients and 139 healthy controls (HC) were included. OCT data was acquired with 1) Spectralis spectral domain OCT (MOGAD (N=66) and HC (N=103)) and 2) Cirrus HD-OCT (MOGAD (N=14) and HC (N=36)). Macular combined ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fibre layer (pRNFL) were quantified. RESULTS: At baseline, GCIPL and pRNFL were lower in MOGAD eyes with a history of ON (MOGAD-ON) compared with MOGAD eyes without a history of ON (MOGAD-NON) and HC (p12 months ago (p

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Myelin-oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder that presents in both adults and children as CNS demyelination. Although there are clinical phenotypic overlaps between MOGAD, multiple sclerosis, and aquaporin-4 antibody-associated neuromyelitis optica spectrum disorder (NMOSD) cumulative biological, clinical, and pathological evidence discriminates between these conditions. Patients should not be diagnosed with multiple sclerosis or NMOSD if they have anti-MOG antibodies in their serum. However, many questions related to the clinical characterisation of MOGAD and pathogenetic role of MOG antibodies are still unanswered. Furthermore, therapy is mainly based on standard protocols for aquaporin-4 antibody-associated NMOSD and multiple sclerosis, and more evidence is needed regarding how and when to treat patients with MOGAD. © 2021 Elsevier Ltd

Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ACTRIMS) Forum -- FEB 27-29, 2020 -- West Palm Beach, FL WOS: 000532412600226 … Americas Comm Treatment & Res Multiple Sclerosis

Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ACTRIMS) Forum -- FEB 27-29, 2020 -- West Palm Beach, FL WOS: 000532412600227 … Americas Comm Treatment & Res Multiple Sclerosis

35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) / 24th Annual Conference of Rehabilitation in MS -- SEP 11-13, 2019 -- Stockholm, SWEDEN Nakashima, Ichiro/0000-0002-2612-8948 WOS: 000485303100083 … European Comm Treatment & Res Multiple Sclerosis, Congrex Switzerland Ltd Alexion PharmaceuticalsFukuda Foundation for Medical TechnologyKayamori FoundationKayamori Foundation of Informational Science AdvancementSENSHIN Medical Research FoundationSasagawa Scientific Research GrantMukai Science and Technology Foundation This trial was supported by Alexion Pharmaceuticals. Dr Berthele reports compensations for clinical trials received by his institution from Alexion Pharmaceuticals, Biogen, Novartis Pharmaceuticals, Roche, Sanofi Genzyme and Teva Pharmaceuticals, and personal fees and non-financial support from Bayer Healthcare, Biogen, Merck Serono, Mylan, Novartis Pharmaceuticals, Roche and Sanofi Genzyme.

35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) / 24th Annual Conference of Rehabilitation in MS -- SEP 11-13, 2019 -- Stockholm, SWEDEN Nakashima, Ichiro/0000-0002-2612-8948 WOS: 000485303103144 … European Comm Treatment & Res Multiple Sclerosis, Congrex Switzerland Ltd Alexion PharmaceuticalsFukuda Foundation for Medical TechnologyKayamori FoundationKayamori Foundation of Informational Science AdvancementSENSHIN Medical Research FoundationSasagawa Scientific Research GrantMukai Science and Technology Foundation; EDEN; GMSI; Guthy-Jackson Charitable Foundation; John Fell Fund; MRCMedical Research Council UK (MRC); MS Society; NIHRNational Institute for Health Research (NIHR); Oxford Health Services Research Committee This trial was supported by Alexion Pharmaceuticals. Dr Berthele reports compensations for clinical trials received by his institution from Alexion Pharmaceuticals, Biogen, Novartis Pharmaceuticals, Roche, Sanofi Genzyme and Teva Pharmaceuticals, and personal fees and non-financial support from Bayer Healthcare, Biogen, Merck Serono, Mylan, Novartis Pharmaceuticals, Roche and Sanofi Genzyme.; Dr Palace is partly funded by highly specialized services to run a national congenital myasthenia service and a neuromyelitis service. She has received support for scientific meetings and fees for advisory work from Abide, Alexion, ARGENX, Bayer Schering, Biogen Idec, Chugai Pharma, EuroImmun, Genzyme, MedDay, MedImmune, Merck Serono, Novartis, Roche and Teva, and grants from Abide, Bayer Schering, Biogen Idec, Merck Serono, Novartis and Teva. She has received grants from EDEN, GMSI, the Guthy-Jackson Charitable Foundation, the John Fell Fund, MRC, the MS Society, NIHR and Oxford Health Services Research Committee for research studies.

35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) / 24th Annual Conference of Rehabilitation in MS -- SEP 11-13, 2019 -- Stockholm, SWEDEN WOS: 000485303101161 … European Comm Treatment & Res Multiple Sclerosis, Congrex Switzerland Ltd Alexion PharmaceuticalsFukuda Foundation for Medical TechnologyKayamori FoundationKayamori Foundation of Informational Science AdvancementSENSHIN Medical Research FoundationSasagawa Scientific Research GrantMukai Science and Technology Foundation This trial was supported by Alexion Pharmaceuticals. Dr Pittock reports grants, personal fees and non-financial support from Alexion Pharmaceuticals; grants from the Autoimmune Encephalitis Alliance and Grifols; and grants, personal fees, non-financial support and other from MedImmune, Inc. Dr Pittock has a patent # 9,891,219 (Application # 12-573942) "Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an Individual that is Aquaporin-4 (AQP4)-IgG Autoantibody Positive".; Dr Palace is partly funded by highly specialized services to run a national congenital myasthenia service and a neuromyelitis service. She has received support for scientific meetings and fees for advisory from Abide, Alexion, ARGENX, Bayer Schering, Biogen Idec, Chugai Pharma, EuroImmun, Genzyme, MedDay, MedImmune, Merck Serono, Novartis, Roche and Teva, and grants from Abide, Bayer Schering, Biogen Idec, Merck Serono, Novartis and Teva. She has received grants from EDEN, GMSI, the Guthy-Jackson Foundation, the John Fell Fund, the MRC, the MS Society, NIHR and Oxford Health Services Research Committee for research studies.; Dr Wingerchuk reports grants from Alexion Pharmaceuticals during the conduct of the study; and personal fees from Biogen, BrainStorm Therapeutics, Caladrius, Celgene, MedImmune, Novartis and ONO Pharmaceutical.

35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) / 24th Annual Conference of Rehabilitation in MS -- SEP 11-13, 2019 -- Stockholm, SWEDEN Nakashima, Ichiro/0000-0002-2612-8948 WOS: 000485303101168 … European Comm Treatment & Res Multiple Sclerosis, Congrex Switzerland Ltd Alexion PharmaceuticalsFukuda Foundation for Medical TechnologyKayamori FoundationKayamori Foundation of Informational Science AdvancementSENSHIN Medical Research FoundationSasagawa Scientific Research GrantMukai Science and Technology Foundation This trial was supported by Alexion Pharmaceuticals. Dr Berthele reports compensations for clinical trials received by his institution from Alexion Pharmaceuticals, Biogen, Novartis Pharmaceuticals, Roche, Sanofi Genzyme, Teva Pharmaceuticals, and personal fees and non-financial support from Bayer Healthcare, Biogen, Merck Serono, Mylan, Novartis Pharmaceuticals, Roche, and Sanofi Genzyme.

Recent biochemical observations have helped redefine antigenic components within the voltage-gated potassium channel (VGKC) complex. The related autoantibodies may be now divided into likely pathogenic entities, which target the extracellular domains of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2), and species that target intracellular neuronal components and are likely non-pathogenic. This distinction has enhanced clinical practice as direct determination of LGI1 and CASPR2 antibodies offers optimal sensitivity and specificity. In this review, we describe and compare the clinical features associated with pathogenic LGI1 and CASPR2 antibodies, illustrate emerging laboratory techniques for antibody determination and describe the immunological mechanisms that may mediate antibody-induced pathology. We highlight marked clinical overlaps between patients with either LGI1 or CASPR2 antibodies that include frequent focal seizures, prominent amnesia, dysautonomia, neuromyotonia and neuropathic pain. Although occurring at differing rates, these commonalities are striking and only faciobrachial dystonic seizures reliably differentiate these two conditions. Furthermore, the coexistence of both LGI1 and CASPR2 antibodies in an individual occurs surprisingly frequently. Patients with either antibody respond well to immunotherapies, although systematic studies are required to determine the magnitude of the effect beyond placebo. Finally, data have suggested that CASPR2 and LGI1 modulation via genetic or autoimmune mechanisms may share common intermediate molecules. Taken together, the biochemical distinction of antigenic targets has led to important clinical advances for patient care. However, the striking syndrome similarities, coexistence of two otherwise rare antibodies and molecular insights suggest the VGKC complex may yet be a common functional effector of antibody action. Hence, we argue for a molecular evolution alongside a clinical and phenotypic re-evaluation.

BACKGROUND: To date, no treatment for neuromyelitis optica (NMO) has been granted regulatory approval, and no controlled clinical studies have been reported. OBJECTIVE: To design a placebo-controlled study in NMO that appropriately balances patient safety and clinical-scientific integrity. METHODS: We assessed the "standard of care" for NMO to establish the ethical framework for a placebo-controlled trial. We implemented measures that balance the need for scientific robustness while mitigating the risks associated with a placebo-controlled study. The medical or scientific community, patient organizations, and regulatory authorities were engaged early in discussions on this placebo-controlled study, and their input contributed to the final study design. RESULTS: The N-MOmentum study (NCT02200770) is a clinical trial that randomizes NMO patients to receive MEDI-551, a monoclonal antibody that depletes CD19+ B-cells, or placebo. The study design has received regulatory, ethical, clinical, and patient approval in over 100 clinical sites in more than 20 countries worldwide. CONCLUSION: The approach we took in the design of the N-MOmentum trial might serve as a roadmap for other rare severe diseases when there is no proven therapy and no established clinical development path.