Biomarkers for interstitial cystitis identified, could lead to the first test

University of Pittsburgh researchers have isolated two biomarkers for interstitial cystitis (IC), a chronic and painful pelvic disease for which there currently is no test. The discovery of these biomarkers could lead to a definitive test for IC and have the potential to lead to new therapies. Results of two studies are being presented today at the annual meeting of the American Urological Association (AUA) in San Antonio, and are published in abstracts 69 and 80 of the AUA proceedings.

“IC is a frustrating disease for patients because, to this point, there is no accurate way of diagnosing the condition. Patients undergo a variety of tests to rule out other diseases, all while experiencing significant pain and discomfort. Only after these tests come back negative, can a doctor make the diagnosis of IC,” said Michael Chancellor, M.D., professor, department of urology, University of Pittsburgh School of Medicine.

“Finding a marker for IC can not only make developing an early test for IC possible, but it can lead to new targeted molecular therapies for the condition,” said Fernando de Miguel, Ph.D., assistant professor of urology at Pitt’s School of Medicine.

In the first study, titled “Identification of Nuclear Proteins in the Chronic Cystitic Rat Model” (abstract 69), researchers used a proteomic approach to identify specific markers related to IC. By comparing protein expression in the bladder tissue of two animal models of IC to expression in the tissue of a normal animal, the researchers found three nuclear proteins that were unique to the animals with IC. Using protein mass fingerprinting, the proteins were identified as transgelin (SM-22), ras suppressor protein (RSU-1) and GAPDH.

In the second study, titled “Time-point study of the Regulation of Nuclear Protein SM-22 (Transgelin) in the Rat Cystitis Model” (abstract 80), the researchers expanded their investigation into the expression of SM-22 in both normal and IC-model bladders. The bladders were instilled with hydrochloric acid; tissue was analyzed at one, four, seven, 13 and 28 days after instillation. After day one and day four, there was a noticeable down-regulation of SM-22 in the IC-model bladders; by day 28, there was a reduction by 31 percent of the SM-22 in the diseased models.

The early down-regulation of SM-22, evident as early as day one, shows that the absence of SM-22 can potentially be used as an early diagnostic marker for IC. The University of Pittsburgh researchers plan to conduct more research into SM-22 to determine the protein’s functional role, which could lead the way to future molecular-targeted therapies.

According to the National Institute of Diabetes and Digestive and Kidney Diseases, 700,000 Americans have IC; 90 percent are women. IC is one of the chronic pelvic pain disorders, defined by recurring discomfort or pain in the bladder and surrounding pelvic region. Symptoms vary and can include any combination of mild to severe pain, pressure and tenderness in the bladder and pelvic area; and an urgent and/or frequent need to urinate. In IC, the bladder wall may become scarred or irritated, and pinpoint bleeding may appear on the bladder wall.

Also contributing to this research were Thu-Suong Van Le, Uukio Hayashi, Shachi Tyagi and Naoki Yoshimura, all from the University of Pittsburgh.