Identification of short-term pharmacodynamic effects of interferon-beta-1a in multiple sclerosis subjects with broad-based phenotypic profiling

We applied broad-based phenotypic profiling to identify phan-nacodynamic markers for interferon-beta in multiple sclerosis subjects. A strong pharmacodynamic effect was observed 1.5 (short-term) vs. 6 days post weekly injection. Hundreds of differences were observed at a p-value <0.001. Most major cell populations, including neutrophils, B cells, CD4 T cells and CD8 T cells, decreased in absolute counts at 1.5 days. The striking exception was motiocytes, which increased substantially. Changes in multiple monocyte-associated cell surface molecules and monocyte related soluble factors were also observed, including: HLA class 11, CCR5, CD38, CD40, CD54, CD64, CD69, CD86, CD101, TLR2, TLR4 and MCP2. These results demonstrate that new hypotheses can be generated from broad molecular and cellular profiling in a clinical setting and provide an approach to identify candidate phannacodynamic markers to evaluate new drug formulations, dosing and bioequivalence. (c) 2007 Elsevier B.V. All rights reserved.