title: Nogo-A Antibodies for Progressive Multiple Sclerosis.
abstract: Most of the current therapies, as well as many of the clinical trials, for multiple sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate potential therapies for the chronic progressive disease stage of MS. The latter is responsible for the steadily increasing disability in many patients, and there is an urgent need for novel therapies that protect nervous system tissue and enhance axonal growth and/or remyelination. As outlined in this review, solid pre-clinical data suggest neutralization of the neurite outgrowth inhibitor Nogo-A as a potential new way to achieve both axonal and myelin repair. Several phase I clinical studies with anti-Nogo-A antibodies have been conducted in different disease paradigms including MS and spinal cord injury. Data from spinal cord injury and amyotrophic lateral sclerosis (ALS) trials accredit a good safety profile of high doses of anti-Nogo-A antibodies administered intravenously or intrathecally. An antibody against a Nogo receptor subunit, leucine rich repeat and immunoglobulin-like domain-containing protein 1 (LINGO-1), was recently shown to improve outcome in patients with acute optic neuritis in a phase II study. Nogo-A-suppressing antibodies could be novel drug candidates for the relapsing as well as the progressive MS disease stage. In this review, we summarize the available pre-clinical and clinical evidence on Nogo-A and elucidate the potential of Nogo-A-antibodies as a therapy for progressive MS.
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland. ineichen@protonmail.ch.|Department of Health Sciences and Technology, ETH Zurich, Zurich, 8057, Switzerland. ineichen@protonmail.ch.
authors.forename: Benjamin V
authors.initials: BV
authors.lastname: Ineichen
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Sciences and Technology, ETH Zurich, Zurich, 8057, Switzerland.
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Plattner
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.|Department of Health Sciences and Technology, ETH Zurich, Zurich, 8057, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Good
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland.|HELIOS Klinik Hagen-Ambrock Department of Neurorehabilitation, Witten/Herdecke University, Faculty of Health, School of Medicine, Ambrockerweg 60, Hagen, 58091, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebank
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland. schwab@hifo.uzh.ch.|Department of Health Sciences and Technology, ETH Zurich, Zurich, 8057, Switzerland. schwab@hifo.uzh.ch.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism; D000070798:Nogo Proteins / Q000276:immunology*
chemical_list: D000906:Antibodies; D007155:Immunologic Factors; D000070798:Nogo Proteins