AFFINERGY, LLC — Department of Health and Human Services SBIR Phase I: 400

Description

SUMMARY ABSTRACT One in ten American adults suffer from chronic kidney diseasewith overend stage renal diseaseESRDpatients receiving hemodialysisHDon a regular basisThe risk of methicillin resistant SaureusMRSAinfections isfold higher in HD patientsand septicemia is the second leading cause of death in this populationThe venous access site is the most common source of these infectionsand due to the high probabability of MRSAit is common practice to empirically treat all suspected Gram positive infections in HD patients with vancomycinHowevervancomycin has a very narrow therapeutic index that must be closely monitoredVancomycin s half life increases fromhours in patients with normal kidney function up tohours in patients with impaired kidney functionwith variable amounts of circulating vancomycin removed by high flux dialysis membranes during each HD sessionUnfortunatelya trial and error dosing strategy remains the standard of care for HD patientsand as a resultsub therapeutic concentrations are found in up toof HD patientsThis often leads to the emergence of vancomycin resistant strains and an increased rate of treatment failureThusin order to maintain an effective circulating vancomycin concentration in HD patientsclinicians need to shift to frequent serum measurementsCompetitive immunoassays are currently used to measure vancomycin levels in a central clinical chemistry labWhile these approaches have sufficient sensitivitythey require specializedexpensive instruments and are not in use at dialysis centersInsteaddialysis patients receiving vancomycin have a blood sample drawn prior to dialysiswhich is then sent to a reference laboratoryBecause the turnaround time for reference lab results can behrspatients are administered the next vancomycin dose prior to knowing whether or not levels should be adjustedThis expands the duration of sub therapeutic dosing bydays and fosters growth of resistant bacterial strains in an already vulnerable hostTo address this technical hurdleAffinergy plans to develop a point of care lateral flow assay that will enable frequentlow complexityaccurate and affordable monitoring of vancomycin levelsUsing our core technology of phage display biopanningwe have already identified a proprietary capture peptide and detection reagent that bind with submicromolar affinity to vancomycinAt the conclusion of Phase Iwe will have a prototype lateral flow assay with established limits of quantitationIn Phase IIwe will scale up production of our assayoptimize performance characteristicsestablish storage conditions and determine stabilityFinallyour assay will be validated in a dialysis patient populationSuccessful completion of this project will lead to improved therapeutic efficacy for dialysis patients receiving vancomycin PROJECT NARRATIVE Vancomycin concentration must be closely monitored in patients with impaired kidney functionHoweverpatients receiving vancomycin during outpatient dialysis must have blood samples shipped to reference laboratories prior to obtaining trough levelsleading to unacceptable delays in vancomycin dosage adjustmentIn this Fast Track applicationwe propose to develop a novel peptide based sandwich assay to facilitate rapidaffordablepoint of care measurement of vancomycin concentration in biological fluids