National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Natcher Building, Room 5AS-13A, 45 Center Drive, MSC 6500, Bethesda, Maryland 20892-6500

A -- MARKERS OF OSTEOARTHRITIS SOL NIH-NIAMS-RFI-99-03 DUE 041999 POC Valerie M. Syed, Contracting Officer, 301-594-2543 The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is seeking sources who have the capability to a) propose potential biochemical markers for osteoarthritis and b) develop, validate, and standardize sensitive assays for osteoarthritis markers in body fluids or tissue specimens. Osteoarthritis is the most prevalent musculoskeletal disorder, characterized by joint pain, tenderness, and functional disability. The percentage of Americans over 65 years of age is the fastest growing segment of the population, which is expected to reach 68 million people by the year 2010. A test for a biochemical marker for osteoarthritis would be particularly useful for early detection, assessment of disease severity and progression or to monitor the effects of therapies. Biomarkers and surrogate endpoints of disease are the focus of an April 15-16, 1999 conference cosponsored by the National Institutes of Health (NIH) and the U.S. Food and Drug Administration (FDA). This forum will emphasize research needs and scientific opportunities to develop and apply biomarkers for safety and efficacy evaluations of novel disease interventions. Markers of joint destruction and repair in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis is one of the topics that will be addressed. More information about this conference is located at the following web address: http://www4.od.nih.gov/biomarkers/. Advances in the molecular biology, biochemistry, and metabolism of cartilage have stimulated the quest for appropriate markers of degradative and regenerative processes in osteoarthritis. In the early stages of osteoarthritis there are marked increases in the catabolism and anabolism of the major cartilage extracellular matrix macromolecules. Important new studies indicate that molecular fragments and metabolites of cartilage-derived matrix molecules are present in the blood and joint fluid in osteoarthritis that have the potential to represent disease-specific markers. The increased rates of cartilage degeneration increase the concentration of matrix components in tissue and body fluids, thus reflecting changes in the rates of cartilage catabolism. Further, changes have been reported in the type or structure of the molecules being newly synthesized by the chondrocytes. Thus, catabolic and anabolic neo-epitopes may be useful markers of metabolic events within the tissue. Markers of metabolic changes in subchondral bone or other joint tissues in osteoarthritis is also of potential interest. Interested sources should provide information addressing the specific technical issues and the capabilities required to undertake this project, including: (1) Existing and new biomarkers for osteoarthritis and their potential significance as surrogates for onset, severity or progression; and (2) The potential methodologies for detection, including production and characterization of reagents and assay systems. Responders may also wish to consider including information about: (3) The anticipated scope of the validation phase to correlate marker concentration to clinical manifestations of osteoarthritis; and (4)The specimen requirements, including identification of tissue or body fluid to be screened, sample amount required, numbers of samples required, and procedures for management and handling of samples. Interested parties should submit a response not to exceed 10 pages addressing the information requested above and summarizing the ability to perform all aspects of the effort described herein. Responses are due by April 19, 1999. Responses will be reviewed only by NIH personnel and will be held in a confidential manner. All proprietary information should be so marked and will be protected. Responses may be submitted by for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, commercial organizations, units of State and local Governments, and eligible agencies of the Federal Government. Collaborative arrangements between the public and private sector are especially encouraged. This announcement is a Request for Information (RFI). The purpose of this RFI is (1) to permit the NIAMS to collect information on the spectrum of markers of potential high value for testing in human patient populations, (2) to determine the number of organizations capable of testing for a biochemical marker for osteoarthritis, and (3) to obtain valuable information that can be used in the development of any future announcements or solicitations if appropriate. All organizations responding to this RFI will receive a copy of any resultant announcement or solicitation. The Government does not intend to award a contract on the basis of responses nor otherwise pay for the preparation of any information submitted or the Government's use of such information. However, should such a requirement materialize, no basis for claims against the Government shall arise as a result of a response to this synopsis or the Government's use of such information as part of the evaluation process or in developing specifications for any subsequent requirement. This requirement is listed under Standard Industrial Classification SIC Code 8731. All respondents are asked to indicate the type and size of their business organization in their response. Inquiries should be directed to Valerie M. Syed, Contracting Officer, Contracts Management Branch National Institute of Arthritis and Musculoskeletal and Skin Disease, 45 Center Drive, Building 45, Room 5AS13A, Bethesda, Maryland 20892. Posted 03/03/99 (W-SN304450). (0062)

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