4.5 Article

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

Journal

JOURNAL OF NEUROIMMUNE PHARMACOLOGY
Volume 6, Issue 1, Pages 158-162

Publisher

SPRINGER
DOI: 10.1007/s11481-010-9226-7

Keywords

multiple sclerosis; interferon-beta; excipients; disaccharides/chemistry

Funding

  1. Aegis Therapeutics, LLC
  2. Nerveda, Inc.
  3. The Johns Hopkins University

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The development of neutralizing antibodies to the protein drug interferon-beta is a significant impediment to its use in the treatment of multiple sclerosis. Neutralizing antibodies to interferon-beta 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-beta in vitro and to reduce its immunogenicity in vivo. Interferon-beta, in solution with and without dodecylmaltoside, was periodically evaluated for aggregation by light scatter for 1 month. Interferon-beta, with and without dodecylmaltoside, was given 3 days/week for 1 month to mice; the sera of these mice were analyzed for anti-interferon-beta antibodies by ELISA. Dodecylmaltoside reduces the aggregation of interferon-beta 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.

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