(Published May 2008)
Current Areas of Research in Interstitial Cystitis/Painful Bladder Syndrome (IC/PBS)
Much remains unknown about interstitial cystitis/painful bladder syndrome (IC/PBS): its etiology and underlying pathophysiology, risk factors for the condition, diagnosis, and optimal management. Current areas of study include:
- Antiproliferative factor
- Intravesical resiniferatoxin
- Gene therapy delivery of preproenkephalin
- Sacral nerve stimulation
- Intravesical botulinum toxin type A
- MN-001 (an oral mast cell stabilizer)
- Physical therapy
One of the most challenging aspects of IC/PBS is the lack of biological markers that could be used to make a definitive diagnosis of the condition. Recent study has focused on trying to identify such a marker. Antiproliferative factor (APF) appears to be a likely candidate. Keay and colleagues found that normal bladder cells cultured in the presence of urine from IC/PBS patients were inhibited from proliferating.1 In contrast, similar inhibition did not occur in bladder cells cultured in the presence of urine from control subjects or patients with bacterial cystitis. The researchers identified APF as a possible causal agent and the bladder cells as the source of APF. They also found that patients with IC/PBS had higher levels of urinary APF than healthy controls. Studies are under way to confirm these findings. Other markers that may be promising include heparin-binding epidermal growth factor-like growth factor (HB-EGF) and epidermal growth factor (EGF).2
Other current research is focusing on improved treatment options for IC/PBS. Animal studies of liposomes, which are phospholipid bilayers that can coat the bladder lining, suggest that these may be useful in humans.3 In contrast, trials evaluating intravesical resiniferatoxin, a capsaicin analogue, have not been encouraging.
Three other agents, URG-101, intravesical botulinum toxin type A, and MN-001, an oral mast cell stabilizer, are under study.4-6 Preliminary studies of the potential for the delivery of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and epidermal growth factor (EGF: a precursor of enkephalin opioids) by gene therapy to the peripheral nerves of the bladder are currently under way. Additional studies of sacral nerve stimulation are needed to determine specifi c groups in whom this treatment is most likely to be effective. Finally, physical therapy is currently under pilot study through NIDDK.1
Research is needed to investigate several different IC/PBS-related areas. The most pressing may be research to:
- Clarify the etiology of IC/PBS to help in the development of effi cacious treatments
- Identify biological markers
- Investigate and agree upon a standard defi nition for IC/PBS to improve diagnosis and epidemiological study
- Gather epidemiological information to better understand the scope and impact of IC/PBS on patients, their families, and society
- Quantify costs associated with IC/PBS
- Explore relationships between IC/PBS and associated conditions
- Keay SK, Szekely Z, Conrads TP, Veenstra TD, Barchi JJ, Jr, Zhang CO, et al. An antiproliferative factor from interstitial cystitis patients is a frizzled 8 protein-related sialoglycopeptide. Proc Natl Acad Sci USA. 2004;101:11803-8.
- Zhang CO, Li ZL, Kong CZ. APF, HB-EGF, and EGF biomarkers in patients with ulcerative vs. non-ulcerative interstitial cystitis. BMC Urology. 2005;5. Available at: http://www.biomedcentral.com/1471-2490/5/7. Accessed June 13, 2007.
- Chancellor M, Yoshimura N. Treatment of interstitial cystitis. Urology. 2004;63 (Suppl A):85-92.
- A randomized multicenter double-blind CT to evaluate the effi cacy and safety of mycophenolate mofetil…(ICCRN RCT2). Available at: http://clinicaltrials-nccs.nlm.nih.gov/ct/show/NCT00451867;jsessionid=8813D8FD370F6E04F3CA AC7290465607?order=2. Accessed June 19, 2007.
- Phase II study to evaluate the effi cacy and safety of two dosing regimens of MN-001 in patients with interstitial cystitis. Available at: http://clinicaltrials. gov/ct/show/NCT00295854?order=5. Accessed June 19, 2007.
- MediciNova announces results from a phase II/III interstitial cystitis trial with MN-001. [press release]. January 16, 2007. Available at: http://www.primenewswire.com/newsroom/news.html?d=111885. Accessed June 19, 2007.
- Physical therapy trial for pelvic pain. Available at: http://clinicaltrials.gov/ct/ show/NCT00434343?order=15. Accessed July 17, 2007.