SBIR-STTR Award

Type 1 Diabetes (T1D) affects an estimated one in three hundred young people in the U.S., with increasing annual incidence. It is primarily an autoimmune disease and is often associated with other serious autoimmune conditions such as Addison's, celiac, and thyroid diseases. Current diagnostic protocols use radioactivity-based assays, measuring multiple autoimmune markers individually. There is a need for the development of better tests to diagnose/predict who will develop T1D, and for monitoring disease progression and therapeutic responsiveness, especially once effective treatments to prevent or delay T1D become available. The completion of the proposed SBIR project, carried out in collaboration with Drs. Yu and Eisenbarth (Barbara Davis Center for Childhood Diabetes), will result in development of sensitive multiplexed assay panels with required sensitivity and specificity for identification of pre-diabetic or recent onset T1D cases, and detection of associated autoimmune diseases. These panels will use sensitive Meso Scale Diagnostics, LLC. (MSD) MULTI-ARRAY(R) detection technology and will use small volumes of patient blood samples to simultaneously detect multiple autoimmune responses. The arrays will incorporate an MSD(R) technology-based assay for pro-insulin and insulin auto-antibodies (IAA) developed by our collaborators that has been shown to outperform currently used IAA radioimmunoassay in multi-laboratory comparative studies. Following subsequent Phase II and III development, the assay panels will be suitable for widespread use with patient samples, providing high accuracy, reproducibility and throughput at significantly lower costs than current singleplex radioactivity-based methods with their inherent regulatory and radioactive waste management issues. The MSD assay format also lends itself to development of point of care assays, making the screening of large populations possible (e.g. in pediatricians' offices) when therapies for the prevention of diabetes enter clinical practice.

Public Health Relevance:
The goal of this project is to develop blood tests that will identify patients (primarily children and young adults) who will develop, or have developed, type 1 diabetes and a number of associated autoimmune diseases. The diagnostic tests developed using MSD's highly sensitive multiplex technology will enable doctors to move away from current approaches that use much larger amounts of patient samples to measure biomarkers individually and involve use of radioactivity.

Public Health Relevance Statement:
The goal of this project is to develop blood tests that will identify patients (primarily children and young adults) who will develop, or have developed, type 1 diabetes and a number of associated autoimmune diseases. The diagnostic tests developed using MSD's highly sensitive multiplex technology will enable doctors to move away from current approaches that use much larger amounts of patient samples to measure biomarkers individually and involve use of radioactivity.

NIH Spending Category:
Autoimmune Disease; Biotechnology; Diabetes; Pediatric; Pediatric Research Initiative; Prevention

Project Terms:
Acute; Addison's disease; Affect; Affinity; Algorithms; Antibodies; Antigens; assay development; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmune Process; Autoimmune Responses; base; Biological Assay; Biological Markers; Blinded; Blood specimen; Blood Tests; Carboxy-Lyases; Celiac Disease; Centers for Disease Control and Prevention (U.S.); Child; Childhood; clinical practice; cohort; Collaborations; Comparative Study; cost; Detection; Development; Diabetes Mellitus; Diabetes prevention; diabetic; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; effective therapy; Goals; High Prevalence; Immobilization; Immune response; Incidence; Insulin; insulin dependent diabetes mellitus onset; Insulin-Dependent Diabetes Mellitus; International; Iodide Peroxidase; K ATPase; Label; Laboratories; Liquid substance; Measures; Methods; Monitor; Patients; pediatrician; Performance; Phase; Plasma; point of care; Population; prevent; Prevention therapy; Process; Production; programs; Proinsulin; Proteins; Protocols documentation; Qualifying; Radioactive; Radioactive Waste; Radioactivity; Radioimmunoassay; Reproducibility; Risk; Sampling; Screening procedure; Sensitivity and Specificity; Serum; Small Business Innovation Research Grant; Specificity; Standardization; Steroid 21-Monooxygenase; Technology; Testing; Therapeutic; Thyroid Diseases; Thyrotropin Receptor; Training; Transglutaminases; Validation; Waste Management; young adult

Type 1 Diabetes (T1D) affects an estimated one in three hundred young people in the U.S., with increasing annual incidence. It is primarily an autoimmune disease and is often associated with other serious autoimmune conditions such as Addison's, celiac, and thyroid diseases. Current diagnostic protocols use radioactivity-based assays, measuring multiple autoimmune markers individually. There is a need for the development of better tests to diagnose/predict who will develop T1D, and for monitoring disease progression and therapeutic responsiveness, especially once effective treatments to prevent or delay T1D become available. The completion of the proposed SBIR project, carried out in collaboration with Drs. Yu and Eisenbarth (Barbara Davis Center for Childhood Diabetes), will result in development of sensitive multiplexed assay panels with required sensitivity and specificity for identification of pre-diabetic or recent onset T1D cases, and detection of associated autoimmune diseases. These panels will use sensitive Meso Scale Diagnostics, LLC. (MSD) MULTI-ARRAY(R) detection technology and will use small volumes of patient blood samples to simultaneously detect multiple autoimmune responses. The arrays will incorporate an MSD(R) technology-based assay for pro-insulin and insulin auto-antibodies (IAA) developed by our collaborators that has been shown to outperform currently used IAA radioimmunoassay in multi-laboratory comparative studies. Following subsequent Phase II and III development, the assay panels will be suitable for widespread use with patient samples, providing high accuracy, reproducibility and throughput at significantly lower costs than current singleplex radioactivity-based methods with their inherent regulatory and radioactive waste management issues. The MSD assay format also lends itself to development of point of care assays, making the screening of large populations possible (e.g. in pediatricians' offices) when therapies for the prevention of diabetes enter clinical practice.

Public Health Relevance Statement:
The goal of this project is to develop blood tests that will identify patients (primarily children and young adults) who will develop, or have developed, type 1 diabetes and a number of associated autoimmune diseases. The diagnostic tests developed using MSD's highly sensitive multiplex technology will enable doctors to move away from current approaches that use much larger amounts of patient samples to measure biomarkers individually and involve use of radioactivity.

NIH Spending Category:
Autoimmune Disease; Biotechnology; Diabetes; Pediatric; Prevention

Project Terms:
Acute; Addison's disease; Affect; Affinity; Algorithms; Antibodies; Antigens; assay development; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmune Process; Autoimmune Responses; base; Biological Assay; Biological Markers; Blinded; Blood specimen; Blood Tests; Carboxy-Lyases; Celiac Disease; Centers for Disease Control and Prevention (U.S.); Child; Childhood; clinical practice; cohort; Collaborations; Comparative Study; cost; Detection; Development; Diabetes Mellitus; Diabetes prevention; diabetic; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; effective therapy; Goals; High Prevalence; Immobilization; Immune response; Incidence; Insulin; insulin dependent diabetes mellitus onset; Insulin-Dependent Diabetes Mellitus; International; Iodide Peroxidase; K ATPase; Label; Laboratories; Liquid substance; Measures; Methods; Monitor; Patients; pediatrician; Performance; Phase; Plasma; point of care; Population; prevent; Prevention therapy; Process; Production; programs; Proinsulin; Proteins; Protocols documentation; Qualifying; Radioactive; Radioactive Waste; Radioactivity; Radioimmunoassay; Reproducibility; Risk; Sampling; screening; Sensitivity and Specificity; Serum; Small Business Innovation Research Grant; Specificity; Standardization; Steroid 21-Monooxygenase; Technology; Testing; Therapeutic; Thyroid Diseases; Thyrotropin Receptor; Training; Transglutaminases; Validation; Waste Management; young adult