Research Project
9046682
? DESCRIPTION (provided by applicant): This project entails the development of a novel dual-component MRI contrast agent formulation for the detecting permeability in the luminal surface of the urinary bladder. The purpose of having such a test is ultimately to allow clinicians, in certain circumstances, to differentially diagnose a chronic, non-infectious inflammation of the urinary bladder from a pelvic floor defect. The two components of the formulation permit the simultaneous tracking of the bladder wall via one component that is composed of particles having a larger particle size, as well as map the local permeability of the wall via the second component composed of particles having a much smaller particle size, wherein each of the two components can be tracked independently. The proposed project is segmented into two aims. The first aim is an animal protocol where bladder wall permeability can be chemically influenced, and the second aim is a pilot clinical protocol designed to assess the feasibility of a human diagnostic test. For aim 1, a mouse model that works well with the available bladder instillation and animal imaging equipment is proposed. Protamine sulfate is the proposed drug for inducing bladder wall permeability, not necessarily because it is the best model of bladder disease, but because it provides the best-controlled inflammatory effects in the time frames logistically available for the proposed imaging experiments. Different levels of permeability induction as well as different levels of bladder distension are proposed as effectors to be tested. Since the components used in the formulation are already FDA-approved for parenteral route of administration, IND approval to study true cystitis in human subjects will be available. This proposal thus includes aim 2, the test of clinical feasibility in six human subjects. These six human sub- jects are divided into three cohorts: two healthy control subjects, two subjects with interstitial cystitis bladder pain syndrome (IC/BPS), and two IC/BPS subjects also having Hunner's ulcer. We anticipate that the results of the both aims of this proposed Phase-1 study will provide the foundation for the development of a subse- quent Phase-2 proposal in which we would propose the further clinical development of the formulation and diagnostic method. If successful, this research could ultimately lead to a product that may be helpful in diagnosing inflammatory conditions of the urinary bladder, such as IC/BPS, a diagnostic test which has been long sought after by the urology community.
