SBIR-STTR Award

Inflammatory Bowel Disease (IBD) remains an intractable chronic disease affecting nearly a quarter million individuals in the United States. A persistent inflammatory reaction is an integral component of this disease. Radiologic, endoscopic and pathologic examination of biopsy specimens are the current accepted approach for its diagnosis. While this is an essential set of procedures for confirming a diagnosis of IBD, it remains an invasive and extensive strategy for screening subjects and for frequent follow-up of established cases. Recent technological advances in the exfoliative biology of the colon have shown that colonic cells and inflammatory cells could be recovered in a viable state from stoop samples and examined for markers of colonic disease. It is now possible to apply this non-invasive approach to screen patients suspected of having IBD by demonstrating the presence of inflammatory cells in stools using two-color immunofluorescent flow cytometry of isolated cells. This new emerging science of COPROCYTOBIOLOGY, involving the isolation of cells from stool and screening, these cell populations for markers of colonic pathology (e.g. Malignancy, ID) is an exciting development. The objective of this SBIR, is to provide proof of concept demonstration for the reliable isolation of inflammatory cells from fecal isolates from stools of patients with IBD. The hypothesis is that inflammatory cells co- express CD-45 (the lymphoid lineage-specific, leucocyte common antigen) and COX-2 (prostaglandin endoperoxidase synthase). Enumeration of these cells by two-color immunofluorescent flow cytometry provides a means of developing an Index of Inflammatory Activity (IIA) which can be used for monitoring epithelial restitution of the colonic mucosa during periods of remission. PROPOSED COMMERCIAL APPLICATIONS: A standardized kit could be made available to clinicians for screening for IBD. The kit can be also used as an inexpensive way for monitoring patients with IBD for clinical response to therapy. Diagnostic laboratories, research centers, biology labs and oncology research centers will be potential users.

Thesaurus Terms:
biomedical equipment development, cytodiagnosis, diagnosis design /evaluation, feces analysis, inflammatory bowel disease, noninvasive diagnosis CD antigen, biomarker, gastrointestinal disorder diagnosis, prostaglandin endoperoxide synthase, ulcerative colitis flow cytometry, human tissue

Inflammatory Bowel Disease (IBD) remains an intractable chronic disease affecting nearly a quarter million individual in the United States. A persistent inflammatory reaction is an integral component of this disease. Radiologic, endoscopic and pathologic examinations of biopsy specimens are the current accepted approach for its diagnosis. While this is an essential set of procedures for confirming a diagnosis of IBD, it remains an invasive and expensive strategy for screening subjects and for frequent follow-up of established cases. Recent technological advances in the exfoliative biology of the colon have shown that colonic cells and inflammatory cells could be recovered in a viable state from stool samples and examined for markers of colonic disease. It is now possible to apply this noninvasive approach to screen patients suspected of having IBD by demonstrating the presence of inflammatory cells in stools by flow cytometry and by PCR amplification of COX-2, the biomarker for the inflammatory response. This new emerging science of coprocytobiology, involving the isolation of cells from stool and screening these cell populations for markers of colonic pathology (eg. malignancy, IBD) is an exciting development. The objective of this SBIR, Phase II is two-fold. The first one is to conduct a double blind cross sectional clinical trial to establish the relationship between IBD disease severity and the expression of GOX-2 in isolated colonocytes and inflammatory cells of lymphoid lineage. The second one is to determine the correlation between indices of clinical findings (GELS, Global Estimates of Lesion Severity) and an Index of Inflammatory Activity (IIA) generated from two sets of outcome measures - ratio of PCR band density COX-2/COX-1 and the ratio COX-2/Cytokeratin l9. The Index of Inflammatory Activity (IIA) may become a non-invasive standard by which physicians can follow IBD patients more frequently for monitoring epithelial restitution of the colonic mucosa during treatment. PROPOSED COMMERCIAL APPLICATION: A standardized kit may become available to clinicians to monitor IBD disease severity by an objective laboratory test. Diagnostic laboratories, research centers, clinical drug trials will be potential users.

Thesaurus Terms:
biomedical equipment development, cytodiagnosis, diagnosis design /evaluation, feces analysis, inflammatory bowel disease, noninvasive diagnosis CD antigen, biomarker, gastrointestinal disorder diagnosis, prostaglandin endoperoxide synthase, ulcerative colitis clinical research, flow cytometry, human subject