Abstract Details

Title A Biological Marker of "Smoldering" Disease Activity in Relapsing-Remitting Multiple Sclerosis in Remission

Topic MS and Related Diseases

Presentation(s) P03 - (-)

Poster/Presentation
Number 244

Objective

Background BACKGROUND: We have discovered a component of plasma that may be suitable for monitoring disease activity in MS. The proteins in this complex are from basement membranes suggesting that it is generated by proteolysis associated with leukocyte entry into the CNS. An increase in MMP-9 activity and its tissue inhibitor TIMP-1 is documented in MS. We postulate that levels of this complex should be inversely related to MMP-9 or TIMP-1 levels.

Design/Methods DESIGN/METHODS: A component of plasma was isolated by salting out and gel filtration and identified by LC-MS. A competitive binding assay was used to quantify the component in plasma. Plasma was obtained from the Barrow Neurology Institute (Phoenix, AZ) and the accelerated cure project (Waltham,MA). Results were analyzed statistically with Fisher's exact test and paired or unpaired t-test.

Results RESULTS: LC-MS showed the complex to be composed of Fibulin-1, Fibronectin and Fibrinogen B chain. RRMS subjects in remission (n= 166) had elevated levels of the complex compared to controls (n=25, p < 0.0001). Untreated RRMS subjects (n= 46) were elevated over controls (p <0.0001). Samples drawn before and after Tysabri treatment were analyzed. Ten of 12 subjects showed a decline in the complex after Tysabri treatment (paired t-test; p= 0.0053). We measured MMP-9 and TIMP-1 levels in MS plasma samples selected for low (MS low), medium (MS medium) or high (MS high) levels of MSDx complex-1. MMP-9 levels did not vary by the complex level but TIMP-1 did. The MShigh group had a low level of TIMP-1 whereas the MSlow group had a high level of TIMP-1 (p=0.0033).

Conclusions CONCLUSIONS: These data suggest that there is a "smoldering" process of tissue invasion during MS remission that can be measured and responds to therapy.

Authors/Disclosures
Ramesh Nayak (MSDx Inc) PRESENTER	No disclosure on file
Roberto Bomprezzi, MD, FAAN (University of Massachusetts, Dept. of Neurology)	Dr. Bomprezzi has nothing to disclose.
	No disclosure on file
Ann D. Bass, MD (Lone Star Neurology - San Antonio)	Dr. Bass has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion, Amgen, Bristol-Myers-Squibb, EMD Serono, Novartis, Roche-Genentech, Sanofi-Genzyme, TG Therapeutics. Dr. Bass has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen, Alexion, EMD Serono, Novartis, Roche-Genentech, Sanofi-Genzyme, TG Therapeutics. Dr. Bass has received personal compensation in the range of $100,000-$499,999 for serving on a Speakers Bureau for Alexion, Amgen, Bristol-Myers-Squibb, EMD Serono, Roche-Genentech, Sanofi-Genzyme, TG Therapeutics. The institution of Dr. Bass has received research support from Bristol-Myers-Squibb, EMD Serono, Novartis, Roche-Genentech, Sanofi-Genzyme, TG Therapeutics.

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