ORIGINAL ARTICLE

Journal of Neuroimmune Pharmacology

, Volume 6, Issue 1, pp 158-162

n-Dodecyl-β-d-Maltoside Inhibits Aggregation of Human Interferon-β-1b and Reduces Its Immunogenicity

  • Robert A. RifkinAffiliated withDepartment of Neurology, The Johns Hopkins University School of Medicine Email author 
  • , Edward T. MaggioAffiliated withAegis Therapeutics, LLC
  • , Sonny DikeAffiliated withDepartment of Neurology, The Johns Hopkins University School of Medicine
  • , Douglas A. KerrAffiliated withBiogen Idec, Inc
  • , Michael LevyAffiliated withDepartment of Neurology, The Johns Hopkins University School of Medicine

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Abstract

The development of neutralizing antibodies to the protein drug interferon-β is a significant impediment to its use in the treatment of multiple sclerosis. Neutralizing antibodies to interferon-β arise from aggregation of the peptide during manufacturing and storage. We tested the ability of dodecylmaltoside, a nontoxic alkylsaccharide surfactant, to reduce aggregation of interferon-β in vitro and to reduce its immunogenicity in vivo. Interferon-β, in solution with and without dodecylmaltoside, was periodically evaluated for aggregation by light scatter for 1 month. Interferon-β, with and without dodecylmaltoside, was given 3 days/week for 1 month to mice; the sera of these mice were analyzed for anti-interferon-β antibodies by ELISA. Dodecylmaltoside reduces the aggregation of interferon-β in vitro and its immunogenicity in vivo. Our positive findings warrant additional tests of dodecylmaltoside as a therapeutic adjuvant in rodent models of multiple sclerosis.

Keywords

multiple sclerosis interferon-beta excipients disaccharides/chemistry