In November 2002, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) issued a request for application (RFA: DK-03-010) for Basic Research in Interstitial Cystitis due. The RFA invited applications for basic cellular, molecular, and genetic research and translational studies focused on understanding the causes and pathogenesis of interstitial cystitis (IC).
New and established investigators from related research areas were invited to apply their knowledge to the study of IC. Related research areas include, but are not limited to, inflammation, epithelial biology, cellular biology, molecular genetics, neuropathology and neurophysiology, the biology and physiology of pain, diagnostic radiology and nuclear medicine, genomics, proteomics, the development of genetic animal models, and autoimmunity. Another highly relevant aim of the RFA was the development of productive research collaborations between investigators with diverse scientific backgrounds. Interstitial Cystitis
Interstitial cystitis (IC) is a debilitating, chronic bladder syndrome consisting of urinary urgency, frequency, and pain in the bladder and surrounding pelvic region. It has been estimated that IC may affect as many as one million American men, women, and children of all ages and races; however, approximately 90 percent of the reported sufferers are women.
Diagnosis of IC is primarily based on symptoms since no currently available blood or urine tests are available because of the lack of demonstrated biological markers. The NIH has established IC diagnostic criteria (Journal of Urology, 140: 203-206, 1988) for use in research studies. IC currently has no consistently effective treatments, and it remains an idiopathic heterogeneous disorder of unknown causes.
A precise etiology for IC has not been demonstrated. Although a number of theories about the pathology of IC exist, none has been scientifically tested and proven. These theories include the possibility of defects in the protective lining of the bladder, an immunogenic or autoimmune disorder, or defects in innervation of the bladder. The possibility that heredity may contribute to susceptibility to IC is another emerging area of interest. The New Basic Research Initiative
The Basic Research in Interstitial Cystitis funding initiative will provide support for basic cellular, molecular, and genetic research and translational studies pertinent to IC from both new and established investigators in relevant fields of investigation. Topics of special interest include, but are not restricted to, the etiology and pathogenesis of IC; innovative diagnostic imaging studies; identification of disease markers and the molecular biology of IC; neurophysiology and bladder innervation and pain pathways; and the genetics of IC susceptibility, causality, and disease progression.
The development of animal models for the study of IC has been an area of special interest, but concern exists that animal models in which bladder pathology is induced through the local administration of irritants may not provide a valid model of human disease. The identification and characterization of new animal models with a genetic predisposition to IC-like syndromes or those generated through transgenic technologies are considered to be of special interest, however.
The goal of the NIDDK in developing this initiative is to support basic and translational studies that will aid in the future development of reliable IC predictive and diagnostic tools, such as blood and urine tests/screen, and new and effective disease treatments and prevention strategies. Achieving the goals outlined in the RFA initiative is deemed a high-priority by the Bladder Research Progress Group (BRPRG)
Remarkable advances have recently been made in the understanding of the molecular and genetic basis of disease. Translational research is the process of applying these ideas, insights, and discoveries to the treatment or prevention of human disease by utilizing the combined research efforts of basic, applied and clinical scientists.
Research areas of special interest and anticipated outcomes or goals include, but are not limited to, the following:
Program Managers: Chris Mullins, Ph.D., Director, Basic Cell Biology
- Etiology and pathogenesis of IC. Especially critical areas of basic IC research are the identification of initial causal factors and factors that influence the course of the disease. Examples of relevant topics include bladder permeability and immunologic and neurogenic factors as related to IC cause and progression. Studies in these areas, as well as new and novel areas of IC cause/pathology, are highly encouraged. Such work might include collaborative research on the cause and pathogenesis of IC and potentially related disorders such as chronic prostatitis, chronic pelvic pain syndrome, irritable bowel syndrome, Crohn's disease, vulvodynia, etc.
- Disease markers and molecular biology of IC. The identification of molecular markers for IC is a critical area of basic research. The identification of disease markers from tissues such as blood and urine is encouraged, though studies of markers from more invasive biopsy samples are also appropriate. Identification of markers may involve a variety of molecular methodologies such as microarray and mass-spectroscopy assessment of gene expression and identification of protein type and levels. Markers that can be used in sensitive, specific tests or screens for IC may prove of immense value in the accurate diagnosis, and even early prediction, of disease. Studies that further describe already reported markers, as well as identify new markers are encouraged.
- Neurological aspects of IC. Studies that investigate the neural properties of relevant cell-types, such as bladder urothelium, and how these properties are altered in IC are encouraged. Studies of bladder afferent neurons are also deemed highly significant. Strongly encouraged areas of study also include the analyses of relevant neurologic cells/tissues and bladder innervation through molecular and imaging strategies, neurophysiology and neuropathology studies, and studies of factors influencing pelvic pain pathways. Investigations in these important areas should provide insight into many particularly debilitating IC symptoms such as urgency, pain associated with bladder filling and urination, and generalized pelvic pain.
- Genetics of IC susceptibility, causality, and disease progression. Evidence exists suggesting a possible genetic basis for IC susceptibility. Studies utilizing existing cohorts of twins would be especially encouraged.
- Application of established and innovative diagnostic and imaging techniques to the study of IC. For example, the development and utilization of radiological and nuclear medicine techniques to visualize and diagnose the urinary bladder affected with IC.
Program, Leroy M. Nyberg, Jr., Ph.D., M.D., Director, Urology Program