SBIR-STTR Award

This SBIR project addresses an important medical need for improved, new technology-based assays for detecting auto antibodies relevant to Type I Diabetes (T1D). T1D affects a million Americans and its incidence is increasing at an alarming rate of 2 to 5% per year. In T1D, circulating auto antibodies against islet cell antigens reflect the process of autoimmune destruction of the insulin-producing beta-cells. Auto antibodies are clinically useful because they are present early in the autoimmune process, often years before patients develop hyperglycemia, and can be used as markers to identify individuals at risk for T1D and to predict risk, particularly when auto antibodies against multiple antigens, are present. Current assays, based on radio immuno adsorbant (RIA) or enzyme linked immunoadsorbant assays (ELISA) methods test for one antibody per assay and are cumbersome, expensive, and some have poor inter-laboratory reproducibility. New intervention strategies for T1D prevention depend on early detection of pre-T1D and sensitive and reliable analytical techniques are crucial. In Phase I, we will test the feasibility of a new multiplex microarray assay based on a novel colloid technology. A microarray format immunoassay will be developed for auto-anti-insulin (IAA), anti- insulinoma associated antigen ( IA-2) and anti-glutamic acid decarboxylase (GAD65)-three autoantibodies informative for T1D. The individual microarray assays will be multiplexed and the multiplex microarray assay performance evaluated relative to current RIA and ELISA assays. We will then evaluate the multiplex microarray assay performance using 25 reference samples. Results of Phase I will demonstrate the feasibility of the novel colloid multiplex micorarray technology as a platform for supporting assays to detect autoantibodies in T1D, and lay the groundwork for full scale development and clinical testing of an efficient, accurate, and reliable T1D clinical diagnostic assay in Phase II. 7. Project Narrative Prediction of T1D through autoantibody testing is critical for the proper identification of individuals at-risk for developing this disease. In T1D, despite the higher risk in relatives, 90% of new cases are sporadic cases occurring in individuals with no prior family history. Thus, in the absence of the capability to screen populations at large, most individuals at risk for T1D are not identified. Clearly, new assays with a better cost-benefit profile are needed to expand the benefit of autoantibody testing. The proposed multiplex microarray methodology is a practical, efficient system to test for T1D autoantibodies. This should allow for the identification of at risk individuals and thus provide a valuable resource for T1D prevention studies

This SBIR project addresses an important medical need for improved, new technology-based assays for detecting autoantibodies relevant to Type 1 diabetes (T1D). T1D affects a million Americans and its incidence is increasing at an alarming rate of 2 to 5% per year. In T1D, circulating autoantibodies against islet cell antigens reflect the process of autoimmune destruction of the insulin-producing beta cells. Auto antibodies are clinically useful because they are present early in the immune process, often years before patients develop hyperglycemia and can be used as markers to identify individuals at risk for T1D and to predict risk, particularly when autoantibodies against multiple antigens are present. Current assays, based on radio immunoadsorbant (RIA) or enzyme linked immunoadsorbant assays (ELISA) methods test for one antibody per assay and are cumbersome, expensive, and some have poor inter-laboratory reproducibility. Recently, a single ELISA assay that is used to detect two antibodies simultaneously but cannot assign antibody specificity became available. New intervention strategies for T1D prevention depend on early detection of pre-T1D and sensitive and reliable analytical techniques are crucial. The Phase I feasibility studies of a new multiplex protein microarray assay, based on our novel colloid technology to simultaneously and specifically detect three autoantibodies i.e. IAA, GAD-65 and IA-2 that are informative for T1D risk, have been very successful. In Phase II, we will develop the "T1D- Autoimmunity Array Testing System" for clinical diagnostic use. The fully integrated system will include disposable assay biochips, an automated processing station that includes a low cost fluorescence reader, sample tracking and analytical soft-ware. At the successful conclusion of Phase II, we will have developed protocols, procedures and the fundamentals of product specifications that will form the basis for production design of the "T1D- AutoimmunityArray Testing System" as a low cost, reliable, accurate testing product that meets the requirements of a broad range of clinical and research environments.

Public Health Relevance:
Prediction of T1D through antibody testing is critical for the proper identification of at-risk subjects and for risk quantification. In T1D, despite the higher risk in relatives, 90% of new cases are sporadic cases occurring in families with no prior family history. Thus, in the absence of the capability to screen populations at large, most children with T1D do not have the opportunity for early treatment unless they are screened because they are related to someone with the disease. Clearly, new assays with a better cost-benefit profile are needed to extend the benefit of autoantibody testing to the majority of individuals who develop T1D and other autoimmune diseases. A multiplex microarray methodology that would allow testing for numerous significant T1D autoantibodies should also allow for early identification of asymptomatic individuals and provide better chances of preventing disease.

Public Health Relevance:
This Public Health Relevance is not available.

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