. Inflammatory Bowel Disease (IBD) is a debilitating chronic condition that affects millions worldwide. Current protocols to monitor disease severity and track response to drugs requires patients to visit clinics, where blood or urine samples are drawn and sent to a central clinical laboratory for processing. This proposal aims to develop point of care user-friendly diagnostics that can be used by patients at home. The strategy is to develop electrochemical assays to monitor inflammatory biomarker levels in urine using repurposed glucose meters. Specifically, Matrixmetalloproteases (MMP) 2 and 9 that are up-regulated and excreted in urine during an acute inflammatory response or flare-ups in IBD patients will be correlated to established laboratory inflammatory biomarkers such as Heamtoxylin and Eosin (H&E) stains and lipocalin-2 (LCN-2) levels.
In specific aim 1, assays to detect MMP 2 and 9 using glucose meters will be developed. Substrates that release an electrochemically active molecule upon the action of MMP 2 or 9 will be generated and a glucose meter will be repurposed to detect the electrochemically active molecule. Selectivity, sensitivity, stability of reagents and other features will be established for this novel assay.
In specific aim 2, the assay will be used to monitor disease progression and response to drugs using an IL10 -/- mouse model, which resembles the physiological, histological and biochemical features of human IBD. Specifically, the degree of inflammation will be assessed using the new noninvasive method and the results compared to invasive methods of H&E stains and LCN-2 levels. Additionally, response to anti TNF-? therapy will be tracked using the different methods. To accomplish these goals, a solid team of scientists with expertise in complementary areas that include chemistry, assay development, molecular biology and clinical diagnostics have been assembled. Successfully executing the specific aims will set the stage for more elaborate studies using patient samples. Self monitoring at home is expected to provide individualized response to therapy and lead to a personalized medicine approach for IBD patients. Results from this strategy can also impact other fields; similar approaches to monitor disease severity and response to treatment for other chronic ailments can be developed.
Disease burden due to Inflammatory Bowel Disease (IBD), a chronic condition with no cure, is significant. This proposal seeks to develop user-friendly point-of-care diagnostics for home use to monitor disease severity and track response to drugs. Regular self-monitoring and communicating the result electronically to the gastroenterologist by patients is expected to lead to a personalized medicine approach that will improve quality of patient care.
