Patented Biomarkers in Infectious Disease

To date, Source MDx has developed Precision Profiles™ for Infectious Disease to reflect host response to various infections caused by individual pathogens. Over 250 technically validated target genes have resulted from extensive literature search, as well as broad in-house experience in whole blood stimulus/challenge studies with non-viable bacteria across various pre-clinical and clinical settings. Precision Profiles™ for Infectious Disease are typically paired with Precision Profiles™ for Inflammation and Immune Response to capture general and disease specific immune system function.

Clinical Studies in Infectious Disease

Sepsis

In 2002 and 2003 Source MDx collaborated with Becton, Dickinson and Company ("BD") and the Maryland Trauma Center in two prospective, longitudinal clinical trials to develop whole blood biomarkers that discriminate systemic inflammatory response syndrome (SIRS) patients from sepsis patients. PAXgene™ Blood RNA Tubes were collected upon admission to the intensive care unit (ICU) and every 24 hours thereafter until patients either tested blood culture positive for sepsis or were released from the ICU (SIRS). Results demonstrated the ability of select biomarkers to differentiate SIRS patients from sepsis patients 48 hours prior to testing blood culture positive. Source MDx patented these predictive biomarkers and granted BD an exclusive diagnostic license in the field of sepsis for commercial development. Source MDx continues to explore research and development opportunities in this area.

Hepatitis C

Source MDx is currently completing an NIH-funded, prospective, longitudinal clinical trial in Hepatitis C (HCV) in collaboration with the University of Colorado Health Sciences Center. The objective of this study is to determine if the clinical manifestation of HCV and patient response/non-response to therapy is reflected in characteristic changes in inflammation-related immune response and disease-specific genes. PAXgene™ Blood RNA Tubes were collected from 30 subjects diagnosed with Hepatitis C prior to and following standard therapy. Gene expression results are anticipated to distinguish HCV patients from healthy normal subjects providing a molecular characterization of host immune response to HCV infection. Furthermore, additional molecular measures characterizing treatment response would serve to improve upon genotype and viral load as predictors of clinical outcome.

Link between Inflammation and Infectious Disease

Source MDx's focus on the characterization of host response to infectious agents is inextricably linked to further downstream interests in viral persistence and resultant chronic inflammatory disorders. This supports foundational work in cancer and inflammation, particularly as clinical and epidemiological data support the association of infectious agents to chronic inflammatory disorders and specific cancers. A selection of relevant references that supports this integrated view is provided below.

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• Feezor RJ et al. Molecular characterization of the acute inflammatory response to infections with gram-negative versus gram-positive bacteria. Infect Immun. 2003 Oct;71(10):5803-13.
• Galiana-Arnoux D et al. Toll-like receptors and innate antiviral immunity. Tissue Antigens. 2006 Apr;67(4):267-76.
• Ishii KJ et al. Host innate immune receptors and beyond: making sense of microbial infections. Cell Host Microbe. 2008 Jun 12;3(6):352-63.
• Jenner RG et al. Insights into host responses against pathogens from transcriptional profiling. Nat Rev Microbiol. 2005 Apr;3(4):281-94.
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• Manger ID et al. How the host 'sees' pathogens: global gene expression responses to infection. Curr Opin Immunol. 2000 Apr;12(2):215-8.
• Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature. 2007 Oct 18;449(7164):819-26.
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