Source MDx (BOULDER, Colorado), a molecular diagnostics company, and Tufts-New England Medical Center (NEMC) (BOSTON, Massachusetts) announced a collaboration to investigate the clinical use of RNA-based molecular diagnostic tests to monitor rheumatoid arthritis (RA) disease status and response to therapy. In conjunction with the Tufts-NEMC study, Source MDx has been awarded a small business innovation research (SBIR) grant by the National Institutes of Health (NIH) to initiate the development of a molecular diagnostic test using RNA-based biomarkers to predict responders and nonresponders to anti-TNF-α therapy for RA. The SBIR grant provides almost $200,000 in funding over a 1-year period and builds on Source MDx's precise gene expression technology and the ability to compare expression levels to a healthy normal range when developing clinically relevant biomarkers of disease. Source MDx will use the SBIR funds to begin to develop a test that identifies patients who will respond best to a defined treatment regimen beginning with characterizing patient response to anti-TNF therapy. Source MDx plans to develop and offer a diagnostic test that provides the earliest warning of disease activity to allow both early intervention before significant joint damage has occurred and adjustment of medications that are not effective.

Researchers at Tufts-NEMC, led by coprincipal investigator, Tim McAlindon, MD, chief of rheumatology at Tufts-NEMC, will manage the clinical studies for a molecular diagnostic test that will characterize RA patients and their response to anti-TNF therapy. Source MDx will provide gene expression analysis of approximately 100 whole blood samples using its patented RA Precision Profileâ„¢ gene panel, designed to diagnose and monitor RA patients, in conjunction with its patented Healthy Normals Reference dataset. Source MDx currently uses this gene expression dataset of 400 healthy blood bank donors as the foundation for its commercial biomarker services.  By the end of this year, the company plans to expand and refine this normals dataset to include over 1000 healthy individuals of diverse age, gender, ethnicity, and geographical location, as well as medical history, hematology and blood chemistry data.

By analyzing biomarkers in whole blood collected from RA patients, Source MDx has already been able to discriminate healthy individuals from patients with RA. Using the same patented process of biomarker analysis, Source MDx will address treatment effectiveness to determine if a therapy is moving the patient toward a "healthier" expression profile. The development of useful RNA-based biomarkers for molecular diagnostics has been hindered in the past by the inability to measure gene expression with sufficient precision, as well as the presumption that gene expression is too variable within and between individuals. Source MDx's proprietary assay technology enables the measurement of gene-expression responses with high precision, which is necessary to give data clinical utility. In addition to RA, Source MDx is developing biomarkers in the following autoimmune diseases: irritable bowel syndrome, lupus, multiple sclerosis (MS), osteoarthritis, and psoriasis. The proprietary technology has already been able to define disease-specific biomarker patterns in blood for several diseases. For RA, a gene panel of 96+ genes has been run in multiple pilot and longitudinal studies, and focused 48 and 24 gene panels have been developed. A 3-gene model has been developed that discriminates between washed-out RA patients and the Healthy Normals Reference dataset. Furthermore, preliminary correlation to disease outcomes has been established. The RA panel was also able to distinguish RA patients from patients with MS. According to Source MDx, a 2-gene model has been developed that perfectly discriminates between RA patients who have failed DMARD (disease modifying anti-rheumatic drug) therapy and the Healthy Normals Reference dataset.

Earlier in 2006, Source MDx and the University of Colorado at Denver and Health Sciences Center (UCDHSC) entered into a research collaboration to develop molecular diagnostic tests for early diagnosis and prognosis of skin diseases, including psoriasis, which was focused on mechanism of action studies with anti-TNF biological agents and other anti-cytokine biological therapeutic agents in chronic plaque psoriasis. The goal of the collaboration is to identify subpopulations of psoriasis patients with different clinical status as well as help clinicians in the future determine which type of anti-TNF agent these patients should receive. The studies are designed to capture gene expression and clinical observation data to stratify skin disease patients into molecular subpopulations to further characterize the disease and develop early diagnosis and prognosis molecular tests.


--A. Techman


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