TY - JOUR
T1 - Restoring immune tolerance in neuromyelitis optica Part I
AU - Steinman, Larry
AU - Bar-Or, Amit
AU - Behne, Jacinta M.
AU - Benitez-Ribas, Daniel
AU - Chin, Peter S.
AU - Clare-Salzler, Michael
AU - Healey, Donald
AU - Kim, James I.
AU - Kranz, David M.
AU - Lutterotti, Andreas
AU - Martin, Roland
AU - Schippling, Sven
AU - Villoslada, Pablo
AU - Wei, Cheng Hong
AU - Weiner, Howard L.
AU - Zamvil, Scott S.
AU - Yeaman, Michael R.
AU - Smith, Terry J.
N1 - Funding Information:
L. Steinman served on the scientific advisory board for Novartis, Recep-tos, Atreca, Tolerion, Teva, received travel funding and/or speaker honoraria from Biogen, Bayhill, Bayer, Celgene, Receptos, is on the editorial board for Multiple Sclerosis Journal, Proceedings of the National Academy of Science, holds a patents for antigen-specific tolerance, has a patent pending for cytokines and type 1 interferons, is on the speakers bureau for EMD Serono, received research support from NIH, has stock options and board membership in Tolerion, is on the board of directors for BioAtla. A. Bar-Or is on the scientific advisory board for Dionix, Receptos-Celgene, Roche/Genentech, Novartis, GSK, Guthy-Jackson Greater Good Foundation, Immune Tolerance Network, received travel funding and/or speaker honoraria from Receptos-Celgene, Roche/Gen-entech, Novartis, Sanofi-Genzyme, GSK, served on the editorial board for Neurology®, Clinical and Experimental Neuroimmunology, consulted for DioGenix, Receptos-Celgene, Roche/Genentech, Novartis, Sanofi-Genzyme, GSK, received research support from Novartis, Sanofi-Genzyme. J.M. Behne and D. Benitez-Ribas report no disclosures. P.S. Chin served as the medical director for Genentech and Novartis Pharmaceuticals Corp. M. Clare-Salzler received research support from NIH, NIAID. D. Healy has a patent pending for the treatment of B cell– mediated autoimmunities with T cell vaccination, has been CSO for Opexa Therapeutics, received research support from and holds stock/ stock options in Opexa Therapeutics. J.I. Kim is an associate editor for the Journal of Negative Results in Biomedicine, is employed by Unum Therapeutics. D.M. Kranz has patents and patents pending in the areas of yeast display and T cell receptor engineering and receives license fee payments from them, consulted for AbbVie, received research support from NIH, Melanoma Research Alliance. A. Lutterotti served on the scientific advisory board for Bayer, Biogen, Novartis, Genzyme, received travel support from European Charcot Foundation, Fundacio GAEM, holds a patent with the University of Zurich, received research support from Wyss Translational Center, Austrian MS Society. R. Martin served on the scientific advisory board for Biogen, Merck Serono, Teva, Genzyme, Sanofi-Aventis, CellProtect, Neuway, received speaker honoraria from Biogen, Merck Serono, Novartis, Roche, Genzyme, holds a patent for the therapeutic efficacy of anto-CD25 monoclonal antibody treatment in combination with IFN-b in MS, consulted for Myelin Repair Foundation, The Weatherall Institute of Molecular Studies, University of Oxford, the Hertie Foundation, is a member of the Kuratorium of the Jung Foundation for Science, received research support from Novartis, Biogen, Swiss National Science Foundation, European Union Seventh Framework Program, European Research Council. S. Schippling served on the scientific advisory board for Bayer Healthcare, Biogen, Merck Serono, Novartis, Sanofi-Genzyme, TEVA, received travel funding and/or speaker honoraria from Bayer Healthcare, Biogen, Merck Serono, Novartis, Sanofi-Aventis, TEVA, is an associate editor for Frontiers in Neurology, holds a patent for therapeutic vaccination in PML using VP1 and Il7, received research support from Sanofi-Genzyme, Novartis, University of Zurich, Betty and David Koetser Foundation for Brain Research, Swiss Multiple Sclerosis Society. P. Villoslada received travel funding and/or speaker honoraria from Novartis, Roche, Genzyme, served as an academic editor for PLoS One, served on the editorial board for Neurology and Therapy, Current Treatment Options in Neurology, Multiple Sclerosis and Demyelinating Disorders, holds a patent for methylthioadenosine for the treatment of MS, Agnostic neurotrophic compounds for the treatment of brain diseases, Gene signature pattern as a biomarker for MS, Algorithm for quantifying fractal dimension in brain MRI, received research support from Novartis, Roche, Genzyme, Instituto de Salud Carlos III, European Commission, National MS Society, Fundacion Maraton TV3, holds stock or stock options in Bionure Inc., Spire Bio-ventures, Mint-Labs. C.-H. Wei reports no disclosures. H.L. Weiner served on the scientific advisory board for the Guthy-Jackson Charitable Foundation, Teva Pharmaceutical Industries, Biogen Idec, Novartis, Sanofi-Aventis, consulted for Therapix, Biogen, Novartis, Serono, Teva, Sanofi, received research support from National Multiple Sclerosis Society. S. Zamvil served on the scientific advisory board for BioMS, Teva Pharmaceuticals, Eli Lilly and Co., Myelin Repair Foundation, is deputy editor for Neurology®: Neuroimmunology & Neuroinflammation, consulted for Biogen Idec, Teva Neuroscience, EMD Serono, Genzyme, Novartis, Roche, is on the speakers bureau for Advanced Health Media, Biogen, received research support from NIH, NMSS, Alexander M. and June L. Maisin Foundation. M.R. Yeaman is on the scientific advisory board for Guthy-Jackson Charitable Foundation, served as an associate editor for PLoS Pathogens, holds patents for Vaccines targeting drug-resistant pathogens, immunotherapies targeting drug-resistant pathogens, novel anti-infective biological therapeutics, novel anti-infective small molecules, novel biological regulating programmed cell death, consulted for Guthy-Jackson Charitable Foundation, received research support from NovaDigm Therapeutics, Inc., Metacin Inc., US Department of Defense, NIH, holds stock or stock options for NovaDigm Therapeutics, Inc., Meta-cin, Inc., receives license fee and royalty payments from NovaDigm Therapeutics. T.J. Smith received research support from NIH, University of South Denmark, Bell Charitable Foundation, RPB Foundation, is a member of the Guthy-Jackson Charitable Foundation scientific advisory board, and holds patents covering the blockade of insulin-like growth factor receptor-l in autoimmune diseases. Go to Neurology.org/nn for full disclosure forms.
Funding Information:
This work was supported in part by the Guthy-Jackson Charitable Foundation.
Publisher Copyright:
© 2016 American Academy of Neurology
PY - 2016
Y1 - 2016
N2 - Neuromyelitis optica (NMO) and spectrum disorder (NMO/SD) represent a vexing process and its clinical variants appear to have at their pathogenic core the loss of immune tolerance to the aquaporin-4 water channel protein. This process results in a characteristic pattern of astrocyte dysfunction, loss, and demyelination that predominantly affects the spinal cord and optic nerves. Although several empirical therapies are currently used in the treatment of NMO/SD, none has been proven effective in prospective, adequately powered, randomized trials. Furthermore, most of the current therapies subject patients to long-term immunologic suppression that can cause serious infections and development of cancers. The following is the first of a 2-part description of several key immune mechanisms in NMO/SD that might be amenable to therapeutic restoration of immune tolerance. It is intended to provide a roadmap for how potential immune tolerance restorative techniques might be applied to patients with NMO/SD. This initial installment provides a background rationale underlying attempts at immune tolerization. It provides specific examples of innovative approaches that have emerged recently as a consequence of technical advances. In several autoimmune diseases, these strategies have been reduced to practice. Therefore, in theory, the identification of aquaporin-4 as the dominant autoantigen makes NMO/SD an ideal candidate for the development of tolerizing therapies or cures for this increasingly recognized disease.
AB - Neuromyelitis optica (NMO) and spectrum disorder (NMO/SD) represent a vexing process and its clinical variants appear to have at their pathogenic core the loss of immune tolerance to the aquaporin-4 water channel protein. This process results in a characteristic pattern of astrocyte dysfunction, loss, and demyelination that predominantly affects the spinal cord and optic nerves. Although several empirical therapies are currently used in the treatment of NMO/SD, none has been proven effective in prospective, adequately powered, randomized trials. Furthermore, most of the current therapies subject patients to long-term immunologic suppression that can cause serious infections and development of cancers. The following is the first of a 2-part description of several key immune mechanisms in NMO/SD that might be amenable to therapeutic restoration of immune tolerance. It is intended to provide a roadmap for how potential immune tolerance restorative techniques might be applied to patients with NMO/SD. This initial installment provides a background rationale underlying attempts at immune tolerization. It provides specific examples of innovative approaches that have emerged recently as a consequence of technical advances. In several autoimmune diseases, these strategies have been reduced to practice. Therefore, in theory, the identification of aquaporin-4 as the dominant autoantigen makes NMO/SD an ideal candidate for the development of tolerizing therapies or cures for this increasingly recognized disease.
UR - http://www.scopus.com/inward/record.url?scp=85016998717&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85016998717&partnerID=8YFLogxK
U2 - 10.1212/NXI.0000000000000276
DO - 10.1212/NXI.0000000000000276
M3 - Review article
AN - SCOPUS:85016998717
VL - 3
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
SN - 2332-7812
IS - 5
M1 - e276
ER -