Urologic Diseases Research Updates
Winter 2007

Research News

Researchers Explore New Frontiers in IC Research

Researchers gathered in Bethesda, MD, last October to share research progress and explore “future frontiers” in the field of basic and clinical interstitial cystitis (IC) research.

The “Basic Research in Interstitial Cystitis: Second Investigators Meeting,” held on October 25, 2006, convened investigators who received funding from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health to promote a range of basic cellular, molecular, and genetic research and translational studies relevant to IC.

“One major goal for the basic science network is to promote increased collaborations and interactions with the clinical community so that the basic science can be even more focused on questions of relevance to developing preventative strategies or clinical treatments,” said Chris Mullins, Ph.D., director of basic cell biology programs in the NIDDK Division of Kidney, Urologic, and Hematologic Diseases.

On October 26 and 27, a broader forum focused on the current research and clinical treatments and where they are headed during the “Frontiers in Painful Bladder Syndrome and Interstitial Cystitis 2006 International Symposium.”

In 2003, the NIDDK began funding the IC Clinical Research Network (ICCRN), a cooperative network of 10 clinical research centers in the United States and Canada, along with one data-coordinating center. The purpose of the ICCRN is to propose, prioritize, develop, and conduct multicenter, clinical trial protocols related to IC and painful bladder syndrome (PBS) treatments and to conduct related ancillary research studies.

Baffling Condition

IC is a chronic, debilitating condition that affects about 1 million people, most of them women. Symptoms include pelvic, bladder, or perineal pain and an urgent and/or frequent feeling of having to urinate, sometimes as often as 18 times a day. Treatments for IC are limited, as are their effectiveness.

Because IC symptoms and severity can vary greatly, most researchers believe IC is not one, but several diseases. In recent years, scientists have started to use the term PBS to describe cases with painful urinary symptoms that might not meet the strictest definition of IC.

The term IC is used alone when describing cases that meet a list of NIDDK-established criteria. The term IC/PBS includes all cases of urinary pain that cannot be attributed to other causes, such as infection or urinary stones.

Difficulties defining IC have contributed to problems in determining IC prevalence, said Philip Hanno, M.D., assistant clinical professor of urology at the Hospital of the University of Pennsylvania, during an epidemiology session on October 26. Wide ranges in prevalence estimates—from 1.6 per 100,000 women to 158 per 100,000 women—can be attributed to lack of a uniform definition of IC/PBS and readily available diagnostic marker(s), unknown etiology, uncertain pathophysiology, lack of standardized methodology, differences in the populations studied, and overlapping conditions and definitions.

Hanno said IC epidemiology could be improved through

• evidence-based, symptom-specific definitions of IC

• studies of true incidence, prevalence, natural history, and risk factors

• the ability to differentiate IC/PBS from other causes of voiding dysfunction and bladder pain

Some of the IC studies underway include

• Events Preceding Interstitial Cystitis (EPIC)—a case-control study involving only women and designed to identify IC/PBS risk factors

• Boston Area Community Health Study—a study to

  • determine the prevalence of PBS by age, gender, race or ethnicity, and socioeconomic status

  • estimate the extent to which PBS symptoms overlap with psychosocial factors, such as sexual abuse or depression

  • determine the relative effects of PBS on quality of life

  • estimate the probable future magnitude of PBS

• RAND IC Epidemiology Study (RICE)—a study to

  • develop a case definition for IC in women for patient screening and epidemiological studies

  • develop and validate a symptom questionnaire to identify female IC patients through self-report

  • develop IC-specific self-report measures of functional status and disease burden

  • conduct first- and second-stage IC screening

  • describe the impact of IC on qualify of life compared with other diseases

Basic Research Progress

One of the goals of the basic research group that met on October 25 “is to gain a greater understanding of the disease at the molecular and cellular level,” said Mullins. “An area that appears to hold promise for understanding the pathophysiology of IC, and possibly for defining the disorder, is biomarker discovery.”

“A number of groups at the meeting presented work that uses cutting-edge approaches to identifying factors that appear differentially regulated in IC cells versus normal cells,” Mullins said. “One such study presented by Brian Liu of Brigham and Women’s Hospital/Harvard Medical School described results identifying a number of autoantibodies that appear to be differentially expressed in IC patients versus non-IC patients, based on a ‘reverse capture’ immunoproteomics approach.”

Other promising areas of research include characterizing urothelial cells and the impact of central nervous system changes on susceptibility to inflammation associated with IC.

Some of the key areas the group identified for further research include

• increased investigation of the cross-sensitization process and better understanding of the central sensitization process, including somato-visceral and viscero-visceral convergence

• greater understanding of the comorbidity of PBS and other disorders

• determining which receptors are involved in bladder mast cell migration

• studies on urothelial differentiation, including molecular and functional markers, translation to clinic, and identifying whether IC subset has aberrant differentiation and if differentiation defects are associated with the disease

• etiopathology of other bladder dysfunctions and the relationship to IC/PBS

• new IC models based on dysfunction of urothelial differentiation, including tissue culture models and new animal models

• urothelial stem cell biology and cell heterogeneity

• development of several hypotheses regarding tissue- and disease-specific targets in IC

• investigations of glycosaminoglycan synthesis and degradation

• intravesical IC therapy challenges

• mechanisms of nociception in IC

• the search for other molecule targets

• case definition and pathogenesis of IC

A report summary of the October 26 to 27 meeting is available at www.niddk.nih.gov/fund/other/niddkfrontiers/frontiers%20in%20PBS%20Summary%20Report.pdf (215 KB).

NIH Publication No. 07–5743
March 2007

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