Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-0005, USA.
J Neuroimmune Pharmacol. 2011 Mar;6(1):158-62. doi: 10.1007/s11481-010-9226-7. Epub 2010 Jun 8.
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.
中和抗体的产生是干扰素-β蛋白药物在多发性硬化症治疗中应用的主要障碍。干扰素-β的中和抗体是由肽在制造和储存过程中的聚集引起的。我们测试了十二烷基麦芽糖,一种无毒的烷基糖苷表面活性剂,减少干扰素-β体外聚集的能力,并降低其体内免疫原性。干扰素-β在含有和不含有十二烷基麦芽糖的溶液中,在 1 个月的时间里定期用光散射法评估聚集情况。有和没有十二烷基麦芽糖的干扰素-β每周给药 3 天,共 1 个月,然后分析这些小鼠的血清中的抗干扰素-β抗体。十二烷基麦芽糖可减少干扰素-β的体外聚集及其体内免疫原性。我们的阳性发现证明了十二烷基麦芽糖作为多发性硬化症啮齿动物模型治疗佐剂的进一步测试是合理的。