Neutralizing Antibodies hinder Multiple Sclerosis therapy

Interferon beta (IFNβ) is used in the treatment of multiple sclerosis (MS). It can reduce the relapse rate and the lesion formation of MRI and slow the progression of the disease. However, some patients develop neutralizing antibodies (NAbs) against interferon beta durin chronic administration of IFNβ. This has been observed in other protein-based drugs in long-term studies as well. Up to 25% of patients treated 3-times-weekly subcutaneously with IFNβ-1a develop Nabs. This could be observed for 2% of the once-weekly treated patients with IFNβ-1a intramuscular. The published data from clinical studies show that the efficacy in patients with NAb-positive compared with those who are NAb negative is reduced. Neutralizing antibodies can potentially cross the blood-brain barrier in IFN-beta-treated patients resulting in relapsing-remitting multiple sclerosis (RRMS) and affect the endogenous IFNβ function within the central nervous system (CNS).  This is confirmed by results of a study by Shapiro et al. It was demonstrated that high serum titers of NAbs (1865-19,320 tenfold reduction units [TRU]) in human astrocytes (in culture) inhibit toll-like receptor-3 ligand and endogenous IFNβ-mediated production of CXCL10 and IL-6. The case study shows that patients with positive titers of NAbs and BAbs in serum did not have detectable NAbs and BAbs that could be detected in the CSF. The absence of these antibodies in the cerebrospinal fluid does not eliminate in general that antibodies may cross the blood-brain barrier locally in the area of inflammation yet nor reach detectable levels in the CSF.

Tags: antibodies, multiple sclerosis, Therapy

This entry was posted on Friday, October 16th, 2009 at 5:03 am and is filed under Therapy. You can follow any responses to this entry through the RSS 2.0 feed.