An Ultrasensitive, High-Throughput, and Low-Cost Autoimmunity Panel for the Early Diagnosis and Improved Treatment of Type 1 Diabetes

用于 1 型糖尿病早期诊断和改进治疗的超灵敏、高通量和低成本自身免疫组合

• 批准号: 9559575
• 负责人: David Seftel
• 金额: $ 74.98万
• 依托单位: ENABLE BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9559575
• 关键词: Acceleration; Affect; Agglutination; Agreement; American; Antibodies; Autoantibodies; Autoimmune Diseases; Autoimmunity; Automation; Beta Cell; Biological Assay; Biological Sciences; CLIA certified; Cessation of life; Chemistry; Child; Clinical; Color; Comorbidity; Companions; Consumption; DNA; DNA Probes; DNA Sequence; Data; Decentralization; Detection; Development; Devices; Diabetes Mellitus; Diabetes autoantibodies; Diabetic Ketoacidosis; Diagnosis; Diagnostic tests; Disease; Early Diagnosis; FDA approved; Funding; General Population; Gold; Hemoglobin; Immunoassay; Insulin; Insulin-Dependent Diabetes Mellitus; Intervention; Islet Cell; Laboratories; Life; Lipids; Liquid substance; Manuals; Methods; Monoclonal Antibodies; Output; Patients; Pediatric Hospitals; Phase; Population; Preventive; Procedures; Process; Production; Quality Control; Radioactive; Radioimmunoassay; Reagent; Reproducibility; Research; Resources; Risk; Risk Assessment; Robotics; Sampling; Sensitivity and Specificity; Serum; Services; Site; Source; System; Technology; Test Result; Testing; Therapeutic; Time; Validation; Variant; Work; base; biobank; clinical diagnostics; cohort; commercialization; cost; design; diabetes control; emergency settings; fluorophore; improved; islet cell antibody; manufacturing process; medical schools; member; novel; pre-clinical; predictive marker; prevent; prototype; quality assurance; screening; screening panel; skills; software development; tertiary care

Type 1 diabetes (T1D) is a devastating autoimmune disease that destroys islet-cell insulin production. Millions of Americans, especially children, are affected and must rely on lifelong insulin administration and struggle with life-threatening co-morbidities. Most new cases of T1D are diagnosed in emergency settings with presentation in potentially deadly diabetic ketoacidosis (DKA). Current pre-clinical diagnostic tests that can permit preventive action for T1D are slow and not readily available outside of tertiary care centers. In this proposal Enable Biosciences will further develop and validate a novel low-cost and high-throughput immunoassay to rapidly and sensitively screen for the four cardinal autoantibody markers that predict risk for type 1 diabetes. Such a test could supplant the current expensive, slow radioactive method. By reducing costs while retaining sensitivity and specificity with a robust very low-sample volume assay, Enable Biosciences' product will permit increased testing to reveal incipient T1D in the general population at the optimal time for intervention. During the Phase I funding period, Enable prototyped a 3-member T1D autoantibody panel using their core Antibody Detection by Agglutination-PCR (ADAP) technology and demonstrated substantial equivalence with the gold-standard assay while removing reliance on radioactive reagents. In this Phase 2 proposal, Enable presents a comprehensive plan to enhance this panel via automation using a dedicated robotic liquid handling system, greatly increasing assay throughput and reliability while further reducing costs. We will also adapt our assay chemistry to be able to use Taqman probes. This will result in further throughput acceleration and cost reductions. Building upon promising preliminary results from Phase 1 work, we will incorporate the fourth and final T1D autoantibody (ZnT8) to create the world's first ever “4-in-1” screening panel, creating a product that provides the highest level of risk assessment for T1D screening and diagnosis. These optimized and automated panels will then be rigorously validated with thousands of clinical samples provided by our wide network of enthusiastic academic and institutional partners that include the Joslin Diabetes Center, Stanford School of Medicine, the T1D Exchange and Tufts Children's Hospital. This data will be used to plan and direct commercialization efforts that will include a phased approach from delivering a CLIA-certified laboratory service to FDA-approved reagent kits with companion integrated sample-to-answer hardware devices for easy, low-skill use and deployment across research and clinical laboratories and screening sites worldwide.

1型糖尿病（T1D）是一种毁灭性的自身免疫性，该糖尿病会影响E型糖尿病，并且必须依靠终身胰岛素给药，并在紧急情况下诊断出潜在致命的糖尿病性疾病中的紧急情况（DKA）。 ）帽子可以在第三级护理中心外面进行预防性，并验证Anow-Cost和高通量的免疫测定法低样本量测定在国际最佳时间，使用核心抗体检测（ADAP）在此阶段2提案中删除的ile。大大提高组装和可靠性，同时降低成本。在T1D筛查和诊断中创建最高的风险评估。医学，T1D交易所和塔夫茨儿童医院。在全球范围内使用和部署跨研究和筛查站点。