MICROBPLEX, INC. — Department of Health and Human Services SBIR Phase I: NIAID

Description

PROJECT SUMMARYLyme disease is the most commonly reported arthropod borne infection in the US with recent CDC estimates eclipsingnew cases inIn addition to growing in frequencythe infections have a complex and increasingly severe courseBeginning with mild flu like symptoms and frequently a signature bull s eye rasherythema migransLyme disease can progress to severe articularneurological and cardiac symptomsmost of which are preventable with early antibiotic therapyLeading investigators have identified two major shortcomings to the current serology based methods for the definitive diagnosis of Early Localized Lyme diseaseFirstthe clinical sensitivity in the first four weeks is poorunderat the time of symptom onsetso many patients remain undiagnosed or unconfirmed until the disease has had time to progressSecondserum antibody levels remain elevated long after the infection has been resolved making the monitoring of therapeutic success or diagnosis of re infection virtually impossibleWe will address these shortcomings by changing the sample matrix that is used for diagnosisEarly in an infection pathogen specific B lymphocytes are activated to form plasmablasts or antibody secreting cellsASCsthat enter and transiently circulate in bloodThese circulating ASCs are present in the blood only during active infection and their numbers decline rapidly when the infection is resolvedBy harvesting ASCsand culturing them in a virgin cell culture mediumthe ASCs create a novel matrixMENSAmedium enriched for newly synthesized antibodyMENSA is an ideal analytical mediumit contains easily measurable quantities of newly synthesizedpathogen specific antibodies and it has no antibodies from prior infectionsASCs emerge into the blood prior to seroconversionso measurement of anti Bburgdorferi antibodies in MENSA will facilitate earlier diagnosis of Lyme diseaseUnlike serum antibodiescirculating ASCs disappear when the infection resolvesso levels of anti Bburgdorferi antibodies in MENSA can be used to track the success of antibiotic therapyMicroB plex and its clinical collaborators have reduced to practice special skills needed to demonstrate these major improvements in Lyme diagnostics using human subjectsThese include definitive commercial ELISAs and custom made high sensitivity anti Bburgdorferi antibody assays validated using a CDC sample panelrecruitment of newly infected subjects in endemic areasshipment of whole blood from clinical sites in Maine and Maryland to Microbplexlaboratory in AtlantaGeorgia for processing and analysisand preliminary data showing that antibody levels in MENSA will track therapeutic successThe two Specific Aims focus directly on early diagnosisAimand tracking therapyAimby following subjects with early Lyme disease through diagnosis and therapy over a period of monthsSuccess will create important new opportunities for diagnosis of Lyme disease and can be extended to other infectious diseases PROJECT NARRATIVE There are more thannew cases of Lyme disease every year in the USLyme disease is a dangerous bacterial infection transmitted by tick bites and it becomes increasingly severe as the infection progressesDefinitive diagnosis is based on serum based tests that have fundamental limitationscurrent tests cannot detect early infections so patients do not receive antibiotic therapy until the infection has progressedandthere is no way to measure if antibiotic therapy has been successfulWe will address these two unmet clinical needs by introducing a novelblood based diagnostic method that will enable clinicians to diagnose infections earlier and to monitor the success of their interventions