958. Biomarker Studies of Interferon-Beta in Mice Following Gene Based Delivery

Interferon beta (IFN-) has been shown to be an effective drug for patients with multiple sclerosis (MS). However dose-dependent side effects from administration of IFN- protein have limited its therapeutic efficacy and clinical utility. IFN- gene therapy offers an alternative approach to overcome these obstacles, and it would be advantageous over bolus delivery of protein. A critical issue in developing such a new approach is in vivo detection of biologically active IFN- in pre-clinical animal models. Several biomarkers have been established in humans undergoing IFN- therapy, including MxA (myxovirus resistant protein) an antiviral protein induced by IFN-. The goal of the present study was to establish and validate a quantitative PCR-based assay to measure RNA expression of Mx1, the murine homologue of human MxA, in peripheral blood mononuclear cells (PBMC) of mice following IFN- protein administration or gene-based delivery. In parallel it was investigated whether IP10, which was recently reported to be up-regulated following IFN- treatment in MS patients, could also be used as biomarker in mice. IP-10 has the advantage that it can be assayed directly by ELISA in plasma samples.