title: Naturally Occurring Monoclonal Antibodies and Their Therapeutic Potential for Neurologic Diseases.
abstract: OBJECTIVE
  Modulating 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.
  
  
  OBJECTIVE
  To review the role of monoclonal, naturally occurring antibodies (NAbs) as novel therapeutic molecules for treatment of neurologic disorders.
  
  
  METHODS
  Peer-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.
  
  
  RESULTS
  Many 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
  Animal 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.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota2Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Bharath
authors.initials: B
authors.lastname: Wootla
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota2Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Jens O
authors.initials: JO
authors.lastname: Watzlawik
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota2Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Warrington
authors.affiliation: Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis4Department of Biomedical Engineering, University of Minnesota, Minneapolis.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Wittenberg
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota2Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Denic
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota2Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis4Department of Biomedical Engineering, University of Minnesota, Minneapolis.
authors.forename: Luke R
authors.initials: LR
authors.lastname: Jordan
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota2Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Louisa M
authors.initials: LM
authors.lastname: Papke
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota2Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Zoecklein
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota2Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Mabel L
authors.initials: ML
authors.lastname: Pierce
authors.affiliation: Department of Electrical and Computer Engineering, University of Minnesota, Minneapolis4Department of Biomedical Engineering, University of Minnesota, Minneapolis.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota2Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Orhun H
authors.initials: OH
authors.lastname: Kantarci
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota2Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, Minnesota5Department of Immunology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Moses
authors.initials: M
authors.lastname: Rodriguez
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D007132:Immunoglobulin Isotypes; D011994:Recombinant Proteins