Phase II year
2020
(last award dollars: 2022)
Phase II Amount
$2,972,995
Lyme disease (LD), caused by the tick-borne bacteria Borrelia, is the most common vector-borne infectious disease in the US with 300,000 new cases annually. If diagnosed early and treated with appropriate antibiotics, outcomes for LD are typically excellent, but delays in treatment result in arthritis, carditis, or neuroborreliosis. The most telling manifestation of early LD is the erythema migrans (EM); however, the EM is often difficult to distinguish from an allergic reaction, and 30% of those infected never develop the rash. Displaying non-specific symptoms which mimic those of other diseases, LD can only be confirmed by laboratory tests. Current laboratory tests rely on serological methods which are ineffective at diagnosing early LD and cannot distinguish between an active and previous infection. Molecular diagnostic tests for direct detection of Borrelia from blood have demonstrated poor sensitivity and have thus not gained traction (or FDA clearance). The end result is that no test today can detect early LD with confidence. To address this unmet need for improved detection of LD, HelixBind has developed RaPID/LD an ultra- sensitive test specifically designed for the direct detection of Borrelia from whole-blood. RaPID/LD displays a limit of detection (LoD) well below a single cell/ml of human blood, orders of magnitude more sensitive than existing molecular diagnostics. RaPID/LD will only detect active infections and incorporates a broad menu of Lyme Disease inducing and Relapsing Fever inducing Borrelia, inclusive of B. miyamotoi, and provides results in roughly 2.5-hours. It has undergone initial testing with clinical specimens and demonstrated superior capabilities. This proposal focuses on: (1) Completing assay development and initial verification testing, (2) Translating the current manual assay to a fully automated test; comprising of single-use plastic devices operated by a small, bench-top, instrument capable of placement in any setting inclusive of the Point-of-Care, and (3) Completing an extensive study with clinical specimens to establish performance metrics. In order to succeed in this endeavor, we have assembled a team of experts in the development of automated diagnostics supported by world-class advisors with expertise in pathology, infectious diseases, clinical microbiology, Lyme Disease, and Borrelia microbiology. Together, we will build upon our capabilities and deliver an automated assay, culminating in a blinded, multi-site, clinical study in collaboration with our clinical partners. Having achieved our Specific Aims, we will begin verification and validation efforts under an ISO 13485 Quality System, scale manufacturing, and complete clinical trials for regulatory clearance. RaPID/LD will represent the initial test for a planned multiplex panel covering a range of tickborne diseases (TBDs).
Public Health Relevance Statement: PROJECT NARRATIVE Rapid and effective diagnosis of Lyme Disease (LD) is an urgent and unmet clinical need. If diagnosed early and treated with appropriate antibiotics, outcomes for LD are typically excellent, but delays in treatment result in arthritis, carditis, or neuroborreliosis. The current standard of care for in-vitro diagnosis, relying on serological tests, lacks both specificity and sensitivity, and cannot distinguish among an active and previous infection. Molecular diagnostic methods for direct detection, while widely appreciated to be the path forward, have persistently demonstrated poor sensitivity. HelixBind will build upon its novel, automated, direct- detection platform, RaPID, and develop the first diagnostic capable of reaching the required performance specifications. The information provided would provide the clinician with objective information on how to identify patients with an active infection weeks before serological test results are useful.
Project Terms: acute infection; Address; Allergic Reaction; Anaplasma phagocytophilum; Antibiotics; Area; Arthralgia; Arthritis; assay development; Babesia; Bacteria; Biological; Biological Assay; Blinded; Blood; Blood Circulation; Blood Volume; Borrelia; Borrelia burgdorferi Group; Borrelia Infections; Borrelia miyamotoi; Budgets; Carditis; Cells; Chronic; Clinic; Clinical; Clinical assessments; Clinical Microbiology; Clinical Research; Clinical Sensitivity; Clinical Trials; Collaborations; Communicable Diseases; cost effectiveness; Data; design; Detection; Development; Devices; Diagnosis; Diagnostic; diagnostic assay; Disease; Early Diagnosis; effectiveness testing; Ehrlichia; Endemic Diseases; Ensure; erythema migrans; Exanthema; experience; Fever; Future; General Population; Gold; Growth; Headache; Health; Hour; Human; Immunoglobulin G; Immunoglobulin M; improved; In Vitro; Infection; innovation; instrument; Intervention; Laboratories; Lutheran Church; Lyme Disease; Manuals; Medical; Medical center; medical schools; member; Methods; Microbiology; Molecular; Molecular Diagnostic Techniques; Molecular Diagnostic Testing; molecular diagnostics; Multi-site clinical study; Myalgia; New England; New York; novel; Order Spirochaetales; Outcome; Pathology; Patients; Performance; Phase; point of care; Recovery; Relapsing Fever; Sampling; Sensitivity and Specificity; Sepsis; Serologic tests; Serological; seropositive; Specimen; standard of care; success; Symptoms; System; Test Result; Testing; tick-borne; Tick-Borne Diseases; tick-borne pathogen; TimeLine; Tissues; Traction; Translating; Vector-transmitted infectious disease; verification and validation; Whole Blood
