CMCC 1634
Highly Sensitive Diagnostic Test for Acute Appendicitis
Inventors: Alex Kentsis, Hanno Steen, Richard Bachur
Categories: Diagnostic/Prognostic
SubCategories: Gastrointestinal/Nutrition, Inflammation
Keywords: Biomarker
CMCC 1634 Image
Receiver operating characteristics of urine protein markers validated by targeted mass spectrometry, demonstrating the relative diagnostic performance of LRG,
calgranulin A (S100-A8), alpha-1-acid glycoprotein 1 (ORM1), and peripheral blood absolute neutrophil count (ANC).
Invention Description:
Acute appendicitis presents a tremendous unmet medical need for rapid differential diagnosis. Over 5% of the population develops appendicitis at some point. Often it first presents in the emergency room, symptoms are indistinct, consequences of misdiagnosis are severe, and increasingly expensive diagnostic tests have become the standard of care. Even with ultrasound and CT scans, anywhere from 3-30% of presentations lead to unnecessary surgeries and 30-45% of appropriate surgeries are delayed until after appendix has ruptured.
In a collaborative project between Emergency Medicine and the Proteomics Center at Children's Hospital, the inventors have identified protein biomarkers in patient urine that distinguish acute appendicitis from other mimicking conditions. The marker discovery was based on deep proteomic analysis of patient urine, assessing over 2000 proteins by mass spectroscopy. These initial putative markers were validated in a large prospective study, and tested for discrimination between acute appendicitis and a dozen inflammatory and non-inflammatory mimicking conditions. The strongest single biomarker, leucine-rich alpha-2-glycoprotein (LRG), demonstarted a 0.97 receiver operating characteristic, area under the curve (a measure of sensitivity and specificity). This protein has not previously been associated with appendicitis, but is associated with inflammatory response. Although the initial identification of the marker used mass spectroscopy, LRG has been detected by immuno-assays in patient urine, and by immunohistochemistry in the appendix, where LRG shows tremendous increase in abundance during the progression of appendix inflammation.
Applications:
Clinical laboratory and point-of-care immuno-assays would be applicable for all emergency care facilities. Placement of the diagnostic test in clinics, doctor's offices and ambulances will speed the referral of emergency cases to the hospital.
Competitive Advantages:
This biomarker is detectable in urine and highly discriminatory for acute appendicitis. It is amenable to development as an immuno-diagnostic assad and a point-of-care immunological test. Such a rapid assessment tools would be tremendously valuable, in reducing expensive diagnostic scans, reducing unnecessary surgeries and reducing the cases that progress to rupture before surgery, all improving patient outcome. This biomarker is more discriminatory than the results reported for other biomarkers under development, and even more discriminatory than ultrasound or CT scans.
Business Opportunity:
Non-exclusive or exclusive license available
Key Publications: Alex Kentsis, Yin Yin Lin, Kyle Kurek, Monica Calicchio, Yan Yan Wang, Flavio Monigatti, Fabien Campagne, Richard Lee, Bruce Horwitz, Hanno Steen, Richard Bachur (2009) "Discovery and Validation of Urine Markers of Acute Pediatric Appendicitis Using High-Accuracy Mass Spectrometry" Annals of Emergency Medicine (In Press, Available online 26 June 2009)
IPStatus: Pat. Pend.