More MS news articles for Oct 2001

MMPs May Be Markers of Treatment Response in MS Patients

WESTPORT, CT (Reuters Health) Oct 29 - Successful treatment with interferon-beta significantly suppresses levels of two matrix metalloproteinases, MMP-7 and MMP-9, in patients with relapsing-remitting multiple sclerosis.

The new findings provide direct evidence of the immunomodulatory effects of interferon-beta in this population and suggest "that MMPs may be considered as potential biomarkers for response to treatment as well as targets for immunotherapy," according to study director Dr. Ariel Miller, of Carmel Medical Center, Haifa, Israel, and a multicenter team.

The researchers examined mRNA levels of multiple MMPs and tissue inhibitors of metalloproteinases (TIMPs) in 16 patients with relapsing-remitting MS and 12 with secondary-progressive MS. They followed six randomly selected patients from each group during 12 months of treatment with interferon-beta.

"Major differences" in MMP and TIMP levels arose between the groups, the investigators report in Annals of Neurology for October. "In the relapsing-remitting MS group, the response to treatment included a significant decrease in MMP-9 and MMP-7 levels, a trend toward a decrease in MMP-2, fluctuations in MT1-MMP and a trend toward a decrease in TIMP-1, in contrast to an increasing trend in TIMP-2 mRNA levels," the team says.

Dr. Miller and associates note that the shift in MMP/TIMP ratios in relapsing-remitting MS patients during treatment with interferon-beta represents a shift from a "pro-proteolytic" profile toward an "anti-proteolytic" profile.

"The inhibition of MMPs' proteolytic activities resulting from interferon-beta treatment may decrease the autoimmune cells' migratory capacity as well as their invasiveness through the blood-brain barrier into the central nervous system, and reduce MMPs-mediated damage to myelin components," they speculate. "These effects of interferon-beta may further prevent the 'epitope-spreading' in the course of the autoimmune process, while promoting CNS repair."

The findings provide new evidence that different immunopathologic mechanisms underlie different forms of MS, the authors conclude, "which may require the use of different therapeutic strategies, among them, as recently suggested, inhibitors of specific MMPs."

Ann Neurol 2001;50:443-451.

Copyright © 2001 Reuters Ltd