Lipella Pharmaceuticals Inc. — Department of Health and Human Services STTR Phase II: 300

Description

ABSTRACT This Phase II SBIR proposal leverages the progress made in Phase I on the development of a novel contrast mixture enhanced Tweighted MRI technique as a safesensitiveand objective diagnostic test for the increased permeability in the luminal surface of the urinary bladder in Interstitial Cystitis Bladder Pain SyndromeIC BPSpatientsThe purpose of having such a test is ultimately to allow cliniciansin certain circumstancesto differentially diagnose a chronicnon infectious inflammation of the urinary bladder from a pelvic floor defectPhase I support was utilized to demonstrate that the novel contrast mixture is superior to individual instillation of either FDA approved gadolinium chelateGadovistor superparamagnetic iron oxide nanoparticlesFerahemein segmenting the rat bladder wall from lumenThe contrast mixture relies on the differences in particle size and contrast mechanisms of the two contrast agents for improved image contrast of the bladder wallGadovist shortens the local Tand Feraheme shortens the local Twherein each of the two components can be tracked independentlyQuantitative Tmeasurements can thus become a biomarker for Gd contrast permeabilityalbeit the quantitative relationship would have to be carefully determinedThe rat studies in Phase I were performed at a high field strength ofTWhen transitioning to imaging of human subjects in clinical field strength scanners atTthe novel contrast mixture was safely tolerated by human subjectswhosemm thick bladder wall could be imaged by a series of single breath hold FLASH sequences in a clinically acceptable imaging timeandlth totalFor Phasethe novel contrast mixture was extemporaneously compoundedand thereforewe need to develop a unit dosage form of novel contrast mixture suitable for an FDA filing and optimize its imaging properties in clinical strength magnet using catWe will also validate the tissue signal enhancement in bladder and perivesical organs by gadolinium measurement by inductively coupled plasma mass spectrometryICP MSOur long term goal is to develop contrast agents for improved patient care of IC patients by optimizingvalidatingand extending quantitative MRI methods for identifying IC patients with bladder permeability versus pelvic floor tonicity PROJECT NARRATIVE Interstitial CystitisBladder Pain SyndromeIC BPSis an incurable chronicdebilitating disease of the urinary bladder that involves urinary urgencyfrequency of urination and chronic pelvic painEstimates of the prevalence of IC BPS in the U Srange fromtocases perpersonsHistoricallyincreased bladder permeability is suggested to be the key determinant of bladder pathology and IC BPS symptomsThere is currently a lack of acceptable methods for direct measurement of bladder permeability in IC BPS patientsand this proposed project will develop a new objective MRI test for direct measurement of bladder permeability