Access the full text.
Sign up today, get DeepDyve free for 14 days.
B. Bacskai, S. Kajdasz, M. McLellan, D. Games, P. Seubert, D. Schenk, B. Hyman (2002)
Non-Fc-Mediated Mechanisms Are Involved in Clearance of Amyloid-β In Vivo by ImmunotherapyThe Journal of Neuroscience, 22
A. Serrano‐Pozo, Christopher William, I. Ferrer, E. Uro-Coste, M. Delisle, C. Maurage, C. Hock, R. Nitsch, E. Masliah, J. Growdon, M. Frosch, B. Hyman (2010)
Beneficial effect of human anti-amyloid-beta active immunization on neurite morphology and tau pathology.Brain : a journal of neurology, 133 Pt 5
D. Boche, J. Donald, S. Love, Scott Harris, J. Neal, C. Holmes, J. Nicoll (2010)
Reduction of aggregated Tau in neuronal processes but not in the cell bodies after Aβ42 immunisation in Alzheimer’s diseaseActa Neuropathologica, 120
J. Dodart, K. Bales, K. Gannon, S. Greene, R. DeMattos, C. Mathis, C. Delong, Su Wu, Xin Wu, D. Holtzman, S. Paul (2002)
Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease modelNature Neuroscience, 5
A. Kermode, A. Thompson, P. Tofts, D. MacManus, B. Kendall, D. Kingsley, I. Moseley, P. Rudge, W. Mcdonald (1990)
Breakdown of the blood-brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications.Brain : a journal of neurology, 113 ( Pt 5)
Xiaohua Xu, A. Denic, Luke Jordan, Nathan Wittenberg, A. Warrington, B. Wootla, Louisa Papke, L. Zoecklein, Daehan Yoo, J. Shaver, Sang‐Hyun Oh, L. Pease, Moses Rodriguez (2015)
A natural human IgM that binds to gangliosides is therapeutic in murine models of amyotrophic lateral sclerosisDisease Models & Mechanisms, 8
Aleksanteri Aspelund, Salli Antila, Steven Proulx, T. Karlsen, Sinem Karaman, M. Detmar, H. Wiig, K. Alitalo (2015)
A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules
V. Keulen, B. Ciric, S. Radhakrishnan, K. Heckman, Yoshihiro Mitsunaga, K. Iijima, H. Kita, Moses Rodriguez, L. Pease (2006)
Immunomodulation using the recombinant monoclonal human B7‐DC cross‐linking antibody rHIgM12Clinical & Experimental Immunology, 143
Nathan Wittenberg, H. Im, Xiaohua Xu, B. Wootla, Jens Watzlawik, A. Warrington, Moses Rodriguez, Sang‐Hyun Oh (2012)
High-affinity binding of remyelinating natural autoantibodies to myelin-mimicking lipid bilayers revealed by nanohole surface plasmon resonance.Analytical chemistry, 84 14
M. Cudkowicz, J. Katz, D. Moore, G. O'neill, J. Glass, H. Mitsumoto, S. Appel, B. Ravina, K. Kieburtz, I. Shoulson, P. Kaufmann, J. Khan, E. Simpson, J. Shefner, B. Levin, V. Cwik, D. Schoenfeld, Swati Aggarwal, M. Mcdermott, Robert Miller (2010)
Toward more efficient clinical trials for amyotrophic lateral sclerosisAmyotrophic Lateral Sclerosis, 11
Brian O'nuallain, R. Hrncic, J. Wall, D. Weiss, A. Solomon (2006)
Diagnostic and Therapeutic Potential of Amyloid-Reactive IgG Antibodies Contained in Human Sera1The Journal of Immunology, 176
R. Watts, M. Dennis (2013)
Bispecific antibodies for delivery into the brain.Current opinion in chemical biology, 17 3
S. Avrameas (1991)
Natural autoantibodies: from 'horror autotoxicus' to 'gnothi seauton'.Immunology today, 12 5
H. Taguchi, S. Planque, Y. Nishiyama, J. Symerský, S. Boivin, P. Szabo, R. Friedland, P. Ramsland, A. Edmundson, M. Weksler, S. Paul (2008)
Autoantibody-catalyzed Hydrolysis of Amyloid β Peptide*Journal of Biological Chemistry, 283
Xiaohua Xu, A. Warrington, Brent Wright, A. Bieber, V. Keulen, L. Pease, Moses Rodriguez (2011)
A human IgM signals axon outgrowth: coupling lipid raft to microtubulesJournal of Neurochemistry, 119
Katerina Papachroni, N. Ninkina, A. Papapanagiotou, G. Hadjigeorgiou, G. Xiromerisiou, A. Papadimitriou, A. Kalofoutis, V. Buchman (2006)
Autoantibodies to alpha‐synuclein in inherited Parkinson’s diseaseJournal of Neurochemistry, 101
E. Kwon, J. Prineas (1994)
Blood‐Brain Barrier Abnormalities in Longstanding Multiple Sclerosis Lesions. An Immunohistochemical StudyJournal of Neuropathology and Experimental Neurology, 53
Jens Watzlawik, R. Kahoud, Shermayne Ng, Meghan Painter, Louisa Papke, L. Zoecklein, B. Wootla, A. Warrington, W. Carey, Moses Rodriguez (2015)
Polysialic acid as an antigen for monoclonal antibody HIgM12 to treat multiple sclerosis and other neurodegenerative disordersJournal of Neurochemistry, 134
R. Boado, Jeff Lu, E. Hui, R. Sumbria, W. Pardridge (2013)
Pharmacokinetics and brain uptake in the rhesus monkey of a fusion protein of arylsulfatase a and a monoclonal antibody against the human insulin receptorBiotechnology and Bioengineering, 110
Jessica Couch, Y. Yu, Yin Zhang, J. Tarrant, R. Fuji, William Meilandt, Hilda Solanoy, Raymond Tong, Kwame Hoyte, W. Luk, Yanmei Lu, K. Gadkar, S. Prabhu, Benjamin Ordonia, Quyen Nguyen, Y. Lin, Zhonghua Lin, M. Balazs, K. Scearce-Levie, J. Ernst, M. Dennis, R. Watts (2013)
Addressing Safety Liabilities of TfR Bispecific Antibodies That Cross the Blood-Brain BarrierScience Translational Medicine, 5
K. Blennow, H. Zetterberg, J. Rinne, S. Salloway, Jenny Wei, R. Black, M. Grundman, E. Liu (2012)
Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease.Archives of neurology, 69 8
Jens Watzlawik, A. Warrington, Moses Rodriguez (2013)
PDGF is Required for Remyelination-Promoting IgM Stimulation of Oligodendrocyte Progenitor Cell ProliferationPLoS ONE, 8
S. McQuaid, P. Cunnea, J. McMahon, Una Fitzgerald (2009)
The effects of blood-brain barrier disruption on glial cell function in multiple sclerosis.Biochemical Society transactions, 37 Pt 1
M. Absinta, P. Sati, M. Gaitán, P. Maggi, I. Cortese, M. Filippi, D. Reich (2013)
Seven‐tesla phase imaging of acute multiple sclerosis lesions: A new window into the inflammatory processAnnals of Neurology, 74
M. Gurney (1997)
The use of transgenic mouse models of amyotrophic lateral sclerosis in preclinical drug studiesJournal of the Neurological Sciences, 152
Moses Rodriguez, V. Lennon, E. Benveniste, Jfan Merrill (1987)
Remyelination by Oligodendrocytes Stimulated by Antiserum to Spinal CordJournal of Neuropathology and Experimental Neurology, 46
C. Barker, R. Billingham (1977)
Immunologically privileged sites.Advances in immunology, 25
B. Wootla, A. Denic, Jens Watzlawik, A. Warrington, Moses Rodriguez (2015)
A single dose of a neuron-binding human monoclonal antibody improves brainstem NAA concentrations, a biomarker for density of spinal cord axons, in a model of progressive multiple sclerosisJournal of Neuroinflammation, 12
Yansheng Du, R. Dodel, H. Hampel, K. Buerger, Suizhen Lin, B. Eastwood, K. Bales, F. Gao, H. Moeller, W. Oertel, Martin Farlow, Steven Paul, Steven Paul (2001)
Reduced levels of amyloid β-peptide antibody in Alzheimer diseaseNeurology, 57
M. Novotná, M. Mateo, P. Soldán, A. Zeid, N. Kale, M. Tutuncu, D. Crusan, E. Atkinson, A. Siva, B. Keegan, I. Pirko, S. Pittock, C. Lucchinetti, J. Noseworthy, B. Weinshenker, Moses Rodriguez, O. Kantarci (2015)
Poor early relapse recovery affects onset of progressive disease course in multiple sclerosisNeurology, 85
R. Doody, Ronald Thomas, M. Farlow, T. Iwatsubo, B. Vellas, S. Joffe, K. Kieburtz, R. Raman, Xiaoying Sun, P. Aisen, E. Siemers, H. Liu-Seifert, R. Mohs (2014)
Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease.The New England journal of medicine, 370 4
F. Gros-Louis, G. Soucy, R. Larivière, J. Julien (2010)
Intracerebroventricular infusion of monoclonal antibody or its derived Fab fragment against misfolded forms of SOD1 mutant delays mortality in a mouse model of ALSJournal of Neurochemistry, 113
M. Soldán, A. Warrington, A. Bieber, B. Ciric, V. Keulen, L. Pease, Moses Rodriguez (2003)
Remyelination-promoting antibodies activate distinct Ca2+ influx pathways in astrocytes and oligodendrocytes: relationship to the mechanism of myelin repairMolecular and Cellular Neuroscience, 22
Robert Miller, J. Mitchell, D. Moore (2012)
Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND).The Cochrane database of systematic reviews, 3
Xiaohua Xu, Nathan Wittenberg, Luke Jordan, Shailabh Kumar, Jens Watzlawik, A. Warrington, Sang‐Hyun Oh, Moses Rodriguez (2013)
A patterned recombinant human IgM guides neurite outgrowth of CNS neuronsScientific Reports, 3
W. Banks, Brie Terrell, S. Farr, S. Robinson, N. Nonaka, J. Morley (2002)
Passage of amyloid β protein antibody across the blood–brain barrier in a mouse model of Alzheimer’s diseasePeptides, 23
D. Gay, M. Esiri (1991)
Blood-brain barrier damage in acute multiple sclerosis plaques. An immunocytological study.Brain : a journal of neurology, 114 ( Pt 1B)
A. Warrington, A. Bieber, B. Ciric, L. Pease, V. Keulen, Moses Rodriguez (2007)
A recombinant human IgM promotes myelin repair after a single, very low doseJournal of Neuroscience Research, 85
D. Morgan (2006)
Immunotherapy for Alzheimer's disease.Journal of Alzheimer's disease : JAD, 9 3 Suppl
A. Louveau, I. Smirnov, Timothy Keyes, Jacob Eccles, S. Rouhani, J. Peske, N. Derecki, D. Castle, James Mandell, Kevin Lee, T. Harris, J. Kipnis (2015)
Structural and functional features of central nervous system lymphaticsNature, 523
I. McKeith, C. Ballard, R. Perry, P. Ince, J. O'Brien, D. Neill, K. Lowery, E. Jaros, R. Barber, P. Thompson, A. Swann, A. Fairbairn, E. Perry (2000)
Prospective validation of Consensus criteria for the diagnosis of dementia with Lewy bodiesNeurology, 54
A. Warrington, A. Bieber, V. Keulen, B. Ciric, L. Pease, Moses Rodriguez (2004)
Neuron‐Binding Human Monoclonal Antibodies Support Central Nervous System Neurite ExtensionJNEN: Journal of Neuropathology & Experimental Neurology, 63
A. Denic, S. Macura, A. Warrington, I. Pirko, B. Grossardt, L. Pease, Moses Rodriguez (2011)
A Single Dose of Neuron-Binding Human Monoclonal Antibody Improves Spontaneous Activity in a Murine Model of DemyelinationPLoS ONE, 6
Y. Mitsunaga, B. Ciric, V. Keulen, A. Warrington, M. Soldan, A. Bieber, Moses Rodriguez, L. Pease (2002)
Direct evidence that a human antibody derived from patient serum can promote myelin repair in a mouse model of chronic‐progressive demyelinating diseaseThe FASEB Journal, 16
O. Kantarci, I. Pirko, Moses Rodriguez (2013)
Novel Immunomodulatory Approaches for the Management of Multiple SclerosisClinical Pharmacology & Therapeutics, 95
A. Burstein, Qinying Zhao, J. Ross, S. Styren, J. Landen, Wendy Ma, F. McCush, C. Alvey, J. Kupiec, M. Bednar (2013)
Safety and Pharmacology of Ponezumab (PF-04360365) After a Single 10-Minute Intravenous Infusion in Subjects With Mild to Moderate Alzheimer DiseaseClinical Neuropharmacology, 36
G. Bloomgren, S. Richman, C. Hotermans, M. Subramanyam, S. Goelz, A. Natarajan, Sophia Lee, T. Plavina, J. Scanlon, A. Sandrock, C. Bozic (2012)
Risk of natalizumab-associated progressive multifocal leukoencephalopathy.The New England journal of medicine, 366 20
R. Pepinsky, Z. Shao, B. Ji, Qin Wang, Gym Meng, L. Walus, X. Lee, Yinghui Hu, Christilyn Graff, E. Garber, W. Meier, S. Mi (2011)
Exposure Levels of Anti-LINGO-1 Li81 Antibody in the Central Nervous System and Dose-Efficacy Relationships in Rat Spinal Cord Remyelination Models after Systemic AdministrationJournal of Pharmacology and Experimental Therapeutics, 339
F. Bard, C. Cannon, R. Barbour, R. Burke, D. Games, H. Grajeda, T. Guido, K. Hu, Jiping Huang, K. Johnson-wood, K. Khan, D. Kholodenko, Mike Lee, I. Lieberburg, R. Motter, M. Nguyen, F. Soriano, N. Vasquez, Kim Weiss, Brent Welch, P. Seubert, D. Schenk, T. Yednock (2000)
Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer diseaseNature Medicine, 6
W. Lang, M. Rodriguez, V. Lennon, P. Lampert (1984)
Demyelination and Remyelination in Murine Viral Encephalomyelitis aAnnals of the New York Academy of Sciences, 436
P. Szabo, N. Relkin, M. Weksler (2008)
Natural human antibodies to amyloid beta peptide.Autoimmunity reviews, 7 6
M. Filippi, M. Rocca, G. Martino, M. Horsfield, G. Comi (1998)
Magnetization transfer changes in the normal appering white matter precede the appearance of enhancing lesions in patients with multiple sclerosisAnnals of Neurology, 43
Stephen Boyden (1966)
Natural antibodies and the immune response.Advances in immunology, 5
J. Orgogozo, S. Gilman, J. Dartigues, Bernard Laurent, M. Puel, L. Kirby, P. Jouanny, B. Dubois, L. Eisner, S. Flitman, B. Michel, M. Boada, A. Frank, C. Hock (2003)
Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunizationNeurology, 61
R. DeMattos, K. Bales, D. Cummins, J. Dodart, S. Paul, D. Holtzman (2001)
Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's diseaseProceedings of the National Academy of Sciences of the United States of America, 98
M Leslie (2015)
Cleanup crew., 347
F. Neff, Xing Wei, C. Nölker, M. Bacher, Yansheng Du, R. Dodel (2008)
Immunotherapy and naturally occurring autoantibodies in neurodegenerative disorders.Autoimmunity reviews, 7 6
Y. Nishiyama, H. Taguchi, M. Hara, S. Planque, Yukie Mitsuda, S. Paul (2014)
Metal-dependent amyloid β-degrading catalytic antibody construct.Journal of biotechnology, 180
I. Pirko, B. Ciric, Jeffrey Gamez, A. Bieber, A. Warrington, Aaron Johnson, D. Hanson, L. Pease, S. Macura, Moses Rodriguez (2004)
A human antibody that promotes remyelination enters the CNS and decreases lesion load as detected by T2‐weighted spinal cord MRI in a virus‐induced murine model of MSThe FASEB Journal, 18
R. Doody, M. Farlow, P. Aisen (2014)
Phase 3 trials of solanezumab and bapineuzumab for Alzheimer's disease.The New England journal of medicine, 370 15
D. Besong-Agbo, E. Wolf, F. Jessen, M. Oechsner, E. Hametner, W. Poewe, M. Reindl, W. Oertel, C. Noelker, M. Bacher, R. Dodel (2013)
Naturally occurring α-synuclein autoantibody levels are lower in patients with Parkinson diseaseNeurology, 80
Jens Watzlawik, E. Holicky, D. Edberg, D. Marks, A. Warrington, Brent Wright, R. Pagano, Moses Rodriguez (2010)
Human remyelination promoting antibody inhibits apoptotic signaling and differentiation through Lyn kinase in primary rat oligodendrocytesGlia, 58
Trang Nguyen, Rebecca Elsner, N. Baumgarth (2015)
Natural IgM Prevents Autoimmunity by Enforcing B Cell Central Tolerance InductionThe Journal of Immunology, 194
ImportanceModulating the immune system does not reverse long-term disability in neurologic disorders. Better neuroregenerative and neuroprotective treatment strategies are needed for neuroinflammatory and neurodegenerative diseases. ObjectiveTo review the role of monoclonal, naturally occurring antibodies (NAbs) as novel therapeutic molecules for treatment of neurologic disorders. Evidence ReviewPeer-reviewed articles, including case reports, case series, retrospective reviews, prospective randomized clinical trials, and basic science reports, were identified in a PubMed search for articles about NAbs and neurologic disorders that were published from January 1, 1964, through June 30, 2015. We concentrated our review on multiple sclerosis, Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis. FindingsMany insults, including trauma, ischemia, infection, inflammation, and neurodegeneration, result in irreversible damage to the central nervous system. Central nervous system injury often results in a pervasive inhibitory microenvironment that hinders regeneration. A common targeted drug development strategy is to identify molecules with high potency in animal models. Many approaches often fail in the clinical setting owing to a lack of efficacy in human diseases (eg, less than the response demonstrated in animal models) or a high incidence of toxic effects. An alternative approach is to identify NAbs in humans because these therapeutic molecules have potential physiologic function without toxic effects. NAbs of the IgG, IgA, or IgM isotype contain germline or close to germline sequences and are reactive to self-components, altered self-components, or foreign antigens. Our investigative group developed recombinant, autoreactive, natural human IgM antibodies directed against oligodendrocytes or neurons with therapeutic potential for central nervous system repair. One such molecule, recombinant HIgM22, directed against myelin and oligodendrocytes completed a successful phase 1 clinical trial without toxic effects with the goal of promoting remyelination in multiple sclerosis. Conclusions and RelevanceAnimal studies demonstrate that certain monoclonal NAbs are beneficial as therapeutic agents for neurologic diseases. This class of antibodies represents a unique source from which to develop a new class of disease-modifying therapies.
JAMA Neurology – American Medical Association
Published: Nov 1, 2015
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.