The goals of mAbDx are to make both immediate and lasting positive impacts on healthcare by developing diagnostic tests for diseases that are currently difficult to diagnose and affect large numbers of patients with serious adverse consequences if left untreated. To accomplish these goals, we have established research collaborations with leading investigators in each of our main focus areas. These collaborations are highly synergistic, as they combine mAbDx’s established abilities in biomarker identification and assay development with the disease-specific expertise and clinical acumen of our research partners.
Systemic Inflammatory Response Syndrome (SIRS)
Trauma is the major cause of death for young adults and up to one-third of all trauma deaths are due to SIRS, which can be initiated not only by post-trauma infection and a robust immune response to pathogen associated molecular patterns (PAMPs) but also by a dysregulated immune response directed at endogenous damage associated molecular patterns (DAMPs). DAMPS are proteins that are normally sequestered within the cell, but which can be released upon tissue injury. In particular, mitochondrial DAMPs (mtDAMPs) have been implicated as major drivers of non-infectious (sterile) SIRS after trauma because they retain inflammatory bacterial characteristics from their evolutionary origin as intracellular symbionts. At present, mtDAMPs and the mechanism of the inflammatory response resulting in DAMP-driven SIRS are poorly understood. We have established a novel approach to identify mtDAMPs as early biomarkers of incipient SIRs and to simultaneously make immunocytochemical reagents and assays for their detection and analysis.
Sepsis (SIRS with documented infection) is one of the most common causes of death in the US and worldwide. In the US alone, sepsis results in over 215,000 deaths annually, accounting for more than 9% of all deaths - approximately the same number of deaths caused by myocardial infarctions. Prompt recognition of sepsis and timing of interventions are critical to its successful management, because anti-sepsis therapies may have benefit at certain stages of the disease yet show no benefit or even have detrimental effects at other stages. Unfortunately, at this time there is no widely accepted, accurate, and rapid diagnostic tool available for early identification and staging of sepsis. Recently, mitochondrial dysfunction has been implicated in both damaging pathologic effects of sepsis and potentially protective physiologic responses. We are investigating mitochondrial involvement in sepsis and the diagnostic utility of rapid assays of mitochondrial function suitable for use with non-invasive sampling at point of care.
Marine Shellfish Vibriosis
Vibrio coralliilyticus (Vc) is a shellfish pathogen that causes serious production disruptions in marine shellfish hatcheries and is currently difficult to detect and manage. We have developed a novel lateral flow immunoassay (LFA), the Vibrio coralliilyticus RapidTest, that can detect Vc contamination of Pacific and Atlantic oysters and are working to determine how best to deploy the test in shellfish hatcheries.
Head and Neck Squamous Cell Carcinoma (HNSCC)
HNSCC is the sixth most common cancer in the US and the world. Early diagnosis is difficult, which contributes to a poor prognosis at diagnosis and a 5 year mortality rate that has remained unchanged over the past 20 years. Because therapy is more effective with early stage disease, a simple reliable diagnostic test that improves early detection of HNSCC could help improve long- term survival. We have identified a new biomarker of HNSCC and are evaluating utility of prototype immunoassays using non-invasive sampling of oral and throat tissues. If effective, such tests could be deployed widely in inexpensive screening programs of high-risk individuals, as HNSCC has been linked with frequent tobacco and alcohol use, infection by human papilloma virus, and extensive consumption of extremely hot drinks.
Inherited Mitochondrial Diseases
Inherited diseases affecting mitochondrial OXPHOS complexes I and IV comprise the largest group of inherited mitochondrial diseases. Although expression of isolated inherited OXPHOS enzyme deficiencies at birth are relatively rare (1:5,000), carriers are much more common (> 1:200) due to the existence of numerous pathogenic mutations (Cree et al., BBA 2009, 1792:1097). The dual genotype genetics (nuclear and mtDNA) and variable expression of OXPHOS deficiencies are complex. In addition, carriers that express sub-clinical deficiencies of these enzymes may be at risk for acquired mitochondrial disorders when exposed later in life to environmental mitotoxins such as certain antibiotics or anti-viral therapeutic drugs, or simply as a result of the ‘normal’ decline in OXPHOS function associated with aging. Heterogeneous populations with sub-clinical deficiencies may also account for many of the often-observed ‘idiosyncratic’ adverse responses exhibited by subpopulations of large groups treated with therapeutic drugs. We are continuing work begun at MitoSciences to determine the utility and optimal deployment of simple point-of- care, non-invasive tests (dipstick assays) to detect small deficits in both enzyme function and protein levels in these enzymes and to eventually better define and alert these at-risk subpopulations.