SBIR-STTR Award

AbaStar MDx RFA-OD-09-009, (R43), SBIR - Gene Expression Exon Array Biomarkers to Diagnose Schizophrenia Project Summary/Abstract This application RFA-OD-09-009, addresses Recovery Act Limited Competition: Small Business Catalyst Awards for Accelerating Innovative Research (R43). The proposal is titled: ""Gene Expression Exon Array Biomarkers to Diagnose Schizophrenia"". The National Institute of Mental Health is specifically seeking the development of biomarkers for psychiatric disorders. AbaStar MDx's long term aim is the development of a novel, innovative, commercially-viable means of genetically diagnosing and differentiating schizophrenia (SZ), bipolar disorder (BD) and Major Depressive Disorder (MDD) from normal/healthy individuals (NC) with mRNA gene expression signatures from a blood sample. Results will address significant clinical issues, provide faster and more accurate diagnoses, add to the understanding of shared and unique pathophysiologies of each disorder. Future success in this effort may alter medical treatment by providing more effective drugs, appropriate early interventions for mental disorders. The specific objective of this pilot study is to demonstrate predictive and, consistent surrogate biomarkers to diagnose SZ with dysregulated mRNA gene expression signature from blood samples at three different time points over three months. We have shown, in NC, 20% of the RNA transcripts measured on Affymetrix exon array were not significantly changed over nine consecutive blood draws time points over 54 hours. The remaining 80% were changed significantly. Well-known episodic nature of the disease might lead to highly variable results depending on when blood is collected in relation to the severity of the disease/symptoms. Variables, such as time of day of the sample collection, day to day variability might have an impact on the expression profile. Also another challenge addressed is that several researchers have confirmed dysregulated RNA genes in blood sample of SZ compared to NC. However, the SZ gene sets don't overlap from one study to the next and to date all samples were collected at one time point. The study would reveal variability of alternative splicing and confirm that we have the best set of biomarker genes for diagnostic product development. These criticisms from prior submissions have been addressed with this study with multiple blood draws from the same individuals over longer time periods to show consistency of the proposed RNA screen. If successful, this unique diagnostic could address a significant clinical problem and lead to the first blood based test for SZ. We will continue to standardize the experimental process, analyze RNA gene expression data, along with covariates and establish the most consistent possible RNA gene expression biomarker set. These chronic dysregulated gene sets for the disorder can be identified in this proposal (and validated in future studies) with these proposed association studies. This will be accomplished by: Enrolling well characterized chronic SZ patients, ages 18-45 with SZ (n=30) and NC (n=30) subjects at one clinical sites in an institutional review board (IRB) approved clinical study; Conducting clinical assessment then collect whole blood samples from SZ and NC subjects at 3- visits, over 3 months; Extracting high quality RNA from the whole blood samples and measuring RNA gene expression using on Affymetrix exon array; Analyzing statistically RNA gene expression data and alternative splicing, along with covariates throughout to control for the likely effects of cell specific expression, psychiatric symptom assessment scales, clinical lab tests, medications, smoking, drug abuse, ethnic, gender, from three time points;and At the Conclusion: Upon completion of Aims, we expect to have identified a set of mRNA transcripts in SZ that are consistently dysregulated compared to NC overtime and thus are best potential biomarkers to develop diagnostic products. The final commercialized products derived from this approach after validation of the biomarker signatures will be CLIA (Clinical Laboratory Improvement Amendments) lab tests ordered by psychiatrists, and ultimately FDA-approved diagnostic kits for use in hospitals and clinical reference labs. This technological innovation will revolutionize diagnoses and therapy for many types of mental disorders, saving lives, ameliorating morbidity, and rewarding patients with substantially better care. , ,

Public Health Relevance:
AbaStar MDx RFA-OD-09-009, (R43), SBIR - Gene Expression Exon Array Biomarkers to Diagnose Schizophrenia Project Narrative The proposed effort is to demonstrate predictive and consistent surrogate biomarkers to diagnose SZ with dysregulated mRNA gene expression signature from blood samples at three different time points over three months. We expect to have identified a set of mRNA transcripts in SZ that are consistently dysregulated compared to NC over time. This will provide the best potential biomarkers to develop diagnostic products. This will establish new standards for treatment decisions for the 2.5 million American adults diagnosed with SZ. This technological innovation will revolutionize diagnoses and therapy for many types of mental disorders. It will also lead to saving lives, ameliorating morbidity, and rewarding patients with substantially better care. If successful, this transforming development will establish a revolutionary platform to address the myriad of other mental disorders affecting 57 million Americans for which no 'objective'clinical test yet exists.

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