Project Grant R44DK141388

DEVELOPING A NOVEL VESICO-AMNIOTIC SHUNT TO TREAT FETAL LOWER URINARY TRACT OBSTRUCTION - PROJECT SUMMARY FETAL LOWER URINARY TRACT OBSTRUCTION (LUTO) IS A SEVERE BIRTH DEFECT THAT RESULTS IN DAMAGE OR MALFORMATION OF THE BLADDER, KIDNEYS, AND LUNGS. LUTO IS ASSOCIATED WITH AN UP TO 80% MORTALITY RISK, AND SURVIVORS CONTINUE TO SUFFER LIFE-LONG COMPLICATIONS ASSOCIATED WITH THEIR KIDNEYS AND URINARY AND PULMONARY SYSTEMS. LUTO CAN BE TREATED BY PERFORMING FETAL SURGERY (USUALLY IN THE SECOND OR THIRD TRIMESTER) TO IMPLANT A VESICOAMNIOTIC SHUNT (VAS). THIS CREATES AN ALTERNATE CHANNEL BETWEEN THE BLADDER AND AMNIOTIC SPACE THAT BYPASSES THE BLADDER OBSTRUCTION, IMPROVES AMNIOTIC FLUID VOLUME, AND RESCUES LUNG DEVELOPMENT DURING GESTATION. EXISTING VAS ARE ASSOCIATED WITH A DISLODGEMENT RATE UP TO 80%, WHICH OFTEN NECESSITATES REPEAT INVASIVE PROCEDURES TO REPLACE THE SHUNT. DUE TO THE RISKS OF THE OPERATION AND ITS HIGH INHERENT FAILURE RATE, VAS TREATMENT IS TYPICALLY PERFORMED IN THE MOST SEVERE LUTO CASES (~10%). THIS INDICATES A LARGE UNMET NEED. VORTEX MEDICAL IS DEVELOPING A NOVEL FETAL VAS THAT INCORPORATES ENHANCED ANCHORS (FIXATION) TO REDUCE DISLODGEMENT, MATERIALS THAT ENHANCE THE SHUNT'S VISIBILITY ON ULTRASOUND TO OPTIMIZE SHUNT DEPLOYMENT, AND A REINFORCED CHANNEL THAT RESISTS KINKING AND CAN EXTEND AS THE FETUS GROWS. WE HAVE PROTOTYPED THE DESIGN AND TESTED THE DEVICE'S PERFORMANCE IN BENCH TESTS AND A PILOT STUDY IN FETAL SHEEP. THESE STUDIES SUGGEST THE VORTEX SHUNT IS SUPERIOR TO CURRENTLY AVAILABLE SHUNTS, DELIVERING PROOF-OF-CONCEPT FOR OUR DESIGN. IN THE PROPOSED FAST-TRACK SBIR PROJECT, WE WILL REFINE THE DESIGN OF THE VORTEX SHUNT AND COMPLETE PRECLINICAL TESTING. IN PHASE I, WE WILL OPTIMIZE THE DESIGN OF THE CONDUIT AND THE METHOD FOR JOINING THE CONDUIT AND ANCHORS. WE WILL SUBJECT PROTOTYPES TO GESTATION-EQUIVALENT FATIGUE AND THEN VERIFY PERFORMANCE TO ENSURE THE DESIGN IS ROBUST TO FETAL MOVEMENTS. SUBSEQUENTLY, WE WILL HOLD A PRE-SUBMISSION MEETING WITH THE FDA TO SOLIDIFY THE PRECLINICAL TESTING PLAN. IN PHASE II, WE WILL OPTIMIZE THE DESIGN OF THE DELIVERY SYSTEM, DEVELOP SCALABLE MANUFACTURING METHODS, CONDUCT VERIFICATION AND VALIDATION TESTING, AND COMPLETE USABILITY STUDIES WITH FETAL SURGEONS IN A SIMULATED CLINICAL ENVIRONMENT. THESE EFFORTS WILL PROVIDE THE FOUNDATION FOR OUR IDE APPLICATION TO THE FDA TO BEGIN FIRST-IN-HUMAN TRIALS. THE VORTEX SHUNT WILL FOLLOW THE SAME REGULATORY PATHWAY AS CURRENT SHUNTS WITH A HUMANITARIAN USE DESIGNATION (HUD). THE PROPOSED EFFORTS WILL LAY THE GROUNDWORK TO BRING THE VORTEX SHUNT ONE STEP CLOSER TO IMPACTING THE LONG-TERM OUTCOMES FOR PRENATAL LUTO PATIENTS. THE VORTEX SHUNT WILL IMPROVE THE EFFICACY OF PRENATAL LUTO TREATMENT, WHICH WILL REDUCE MORTALITY AND COMPLICATIONS AND RESULT IN HEALTHCARE SAVINGS OF MILLIONS OF DOLLARS ANNUALLY IN THE US ALONE. FURTHERMORE, BY IMPROVING THE SAFETY AND RELIABILITY OF VAS THERAPY, IT WILL EXTEND THE POTENTIAL FOR TREATMENT TO MANY PATIENTS WHO CURRENTLY HAVE NO OPTION.