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

Description

SUMMARY ABSTRACT In the United Statesthere are overindividuals living with cystic fibrosisCFCFwhich is caused by a mutation in the cystic fibrosis transmembrane conductance regulatorCFTRis the most common life limiting autosomal recessive disorder in the United Stateswith pulmonary disease serving as the leading cause of morbidity and mortalityIn the lungmutations in CFTR result in impaired mucociliary clearance and cause an increased risk for lung infectionsIn particularinfection by the gram negative bacteria Pseudomonas aeruginosa is associated with increased lung inflammationreduced lung functionincreased lung exacerbationsand reduced life spanPaeruginosa infections are typically treated with the aminoglycoside antibiotic tobramycinOnce a patient is chronically infected with Paeruginosathey take an inhaled form of tobramycin for aday courseevery other monthDespite this targeted treatment against Paeruginosapatients still suffer from lung exacerbationswhich require the administration of intravenous tobramycinWhile tobramycin is an effective antibiotic against Paeruginosait is associated with both nephrotoxicity and ototoxicityTobramycin therapy must therefore be individualizedand therapeutic drug monitoringTDMis necessary to ensure that the dosage is within the appropriate rangeTypicallytobramycin levels are monitored for a trough valuejust prior to the next doseHoweverCF patients demonstrate enhanced clearing of tobramycinIdeallylevels would be taken athoursand the next dose adjusted if trough levels are too highImportantlyan increasing number of patients are choosing to receive their tobramycin infusions at homeThis outpatient approach reduces exposure to hospital borne pathogens and allows patients to workattend school and be close to familyUnfortunatelythis complicates efforts to properly manage tobramycin therapyresulting in wide discordance of monitoring across the countryFor those patients who do receive TDMblood is collected at clinics or by home healthcare nursesand samples are sent to clinical labs for testingprecluding timely dosage adjustmentsThusthere is an unmet need to develop a preciseaffordablepoint of care method to monitor tobramycin in CF patients undergoing outpatient parenteral tobramycin therapyTo address this needAffinergy is developing highly sensitive capture and detection reagents for a one step locking assay that will enable rapidsimpleand affordable monitoring of tobramycin at the point of careIn this Phase I applicationwe will isolate locking reagents which will recognize tobramycin in complex with a capture reagent to rapidly measure tobramycin concentration in bloodand develop a lateral flow assay that will be easily adaptable to the care regimen of home health nursesA point of care tobramycin assay will allow home health nurses and CF clinical pharmacists to perform timelyactionable TDM in patients receiving home parenteral tobramycin therapywhich has the potential to reduce the risk for adverse eventsminimize growth of resistant bacteria and effectively manage pulmonary exacerbations PROJECT NARRATIVE Pulmonary disease is the leading cause of morbidity and mortality for people living with cystic fibrosisPulmonary exacerbations are most often treated with intravenous tobramycin administrationwhich can be performed at homeTobramycin has a narrow therapeutic index and requires drug monitoringwhich is challenging for home therapythereforewe propose to develop a novel assay to facilitate point of care measurement of tobramycin in whole blood