Phase II year
2019
(last award dollars: 2020)
Phase II Amount
$1,487,764
Type 1 diabetes (T1D) is a chronic autoimmune disease that affects millions of children and adults in the US. Up to 40% of T1D patients are diagnosed in the emergency room with life-threatening diabetic ketoacidosis (DKA), resulting in severe clinical complications and a substantial economic burden. Programs that screen for blood-borne markers of early-stage T1D (anti-islet cell autoantibodies) can significantly diminish the incidence of DKA and improve patient quality of life. However, large-scale implementation of such screening campaigns is hindered by the high cost and low throughput of radioimmunoassay (RIA), the gold-standard method for measuring anti-islet autoantibodies. Moreover, a significant portion of screening program costs are associated with phlebotomy, cold-chain storage and shipping. To address this, Enable Biosciences aims to develop a cost-effective, multiplex, high- throughput and non-radioactive immunoassay to diagnose T1D and screen for individuals at risk for T1D using low-cost easy-to-collect dried blood spots (DBS). The successful development of this high- throughput dried blood spot T1D assay can substantially increase the effectiveness of general population- based T1D screening programs. In a JDRF- and Stanford-supported initiative, we were gratified that a serum-based Enable assay achieved the highest performance for anti-GAD, anti-IA2 and a close second-to-highest performance for anti-insulin antibodies in the recent blinded 2018 Islet-cell Autoantibody Standardization Program (IASP) competition out of 50 participating laboratories. The IASP data were generated with an automated Enable serum assay using a custom-made Enable analyzer created in collaboration with Hamilton Robotics. Furthermore, we showed that our manual DBS- based Enable assay correlated strongly with a serum-based assay (R=0.90-0.96). The concordance as evaluated by Cohens test showed kappa between 0.85-0.89. The positive and negative agreements for all three aforementioned autoantibodies range from 85%-99%. Notably, we also demonstrated less than 10% degradation of assay signals when DBS cards were stored at 37°C for 4 weeks. Building on these solid technical achievements, which we consider as our Phase I-like Results described in detail in this proposal, we aim to further automate our DBS assay procedures for high-throughput functionality including DBS elution and DBS eluent testing using diverse samples, such as those from Stanford University School of Medicine. We expect to deliver an integrated DBS T1D autoantibody assay (elution/testing automation device and reagent kits) to serve large screening centers and CLIA- laboratories. We further plan to obtain CE Mark classification and FDA approval to further decentralize DBS T1D autoantibody testing to be able to address the important needs of communities, clinicians and researchers worldwide.
Public Health Relevance Statement: Type 1 diabetes is an incurable autoimmune disease that affects millions of Americans. Screening children and young adults in the general population for their risk of developing type 1 diabetes may help prevent sudden death due to severe disease and help efforts to find a cure. Enable Biosciences is automating methods to measure the presence of blood-borne markers of type 1 diabetes risk using tiny spots of dried blood on paper cards to ease collection, storage and shipping of samples, lowering costs and making it much easier for anyone to get tested while simultaneously helping researchers to develop better therapies.
NIH Spending Category: Autoimmune Disease; Diabetes; Pediatric; Prevention
Project Terms: Accident and Emergency department; Achievement; Address; Adult; Affect; Agglutination; Agreement; American; Antibodies; Autoantibodies; Autoimmune Diseases; Automation; base; Biological Assay; Biological Sciences; Blinded; Blood; Blood Screening; Child; chronic autoimmune disease; Classification; Clinical; Clinical Laboratory Information Systems; cloud based; Cold Chains; Collaborations; Collection; Communities; cost; cost effective; Custom; Data; Decentralization; design; Detection; Development; Devices; Diabetes autoantibodies; diabetes risk; Diabetic Ketoacidosis; Diagnosis; Disease; Economic Burden; Effectiveness; Fingers; General Population; Gold; Immunoassay; improved; Incidence; Individual; Information Systems; Insulin Antibodies; Insulin-Dependent Diabetes Mellitus; islet; Islet Cell; Laboratories; Life; Liquid substance; Manuals; Measures; medical schools; Methods; Modification; Paper; Patients; Performance; Phase; population based; Preparation; prevent; Procedures; Process; program costs; programs; Protocols documentation; quality assurance; Quality of life; Radioimmunoassay; Readiness; Reagent; Research Personnel; Resolution; Risk; robotic system; Robotics; Sampling; screening; screening program; Serum; Shipping; Signal Transduction; Solid; Spottings; Standardization; Sudden Death; System; Testing; Universities; Validation; Venous blood sampling; young adult
