UMG-145

A Transcriptomic Biomarker of Myocarditis

Joshua Hare and Bettina Heidecker

Problem

There is a need to provide early diagnosis and specific treatment of myocarditis (1-3). Myocarditis causes a significant minority of depressed heart function and thus causes heart failure and premature and unexpected sudden cardiac death. Myocarditis affects humans throughout life including children. The current diagnostic approach using histologic analysis of heart tissue obtained by biopsy lacks sensitivity and specificity. There is an urgent need for better biomarkers, to adjust treatment appropriately and at an early stage.

Solution

A molecular signature that functions as a very sensitive diagnostic biomarker for myocarditis, with the possibility of detection via blood sample, would allow physicians to determine the likelihood of a positive diagnosis even in asymptomatic patients.

Competitive Advantage

There is no simple way to predict myocarditis especially in asymptomatic patients. Having access to a unique molecular signature associated with various aspects of cardiac diseases and disorders may allow for identification of patients with myocarditis with a positive predictive value of 80%. This would allow for patient treatment prior to symptoms and would add a huge number of potential patients to the market.

Applications

Simple blood test that will: assess Individual risk aid in the diagnosis of heart disease aid in predicting heart disease even in asymptomatic patients

Patent Status

International Patent Application No. WO2008137595 entitled "A TRANSCRIPTOMIC BIOMARKER OF MYOCARDITIS" was published on November 13, 2008.

Licensing Opportunity

The University of Miami is seeking collaborative research and licensing options.

About the Inventors

Dr. Joshua Hare was recruited from Johns Hopkins University to become chief of cardiology and director of the Interdisciplinary Stem Cell Institute at the University of Miami. Trained at Harvard and Johns Hopkins Hospital, he became a highly productive scientist in the field of heart failure and cardiomyopathies, contributing an enormous amount of work in basic science and clinical research (4-7). Over many years, Dr. Hare and his laboratory has placed a major focus on transcriptomic biomarker research (2;8-10), with the ultimate goal to improve diagnostic and prognostic accuracy in heart failure. In fact, his group published the first proof-of-concept study that transcriptomic biomarkers are feasible in cardiology and can be used to differentiate between the two major forms of cardiomyopathy, ischemic and non-ischemic (11).

Dr. Bettina Heidecker came with Dr. Hare and his team from Hopkins. She conducted her medical thesis on autoimmune mechanisms and heat shock proteins in atherosclerosis in Dr. Georg Wick's laboratory in Innsbruck, Austria. After her graduating with her M.D., she started as a Post-Doctoral Fellow in Dr. Hare's group and specialized in microarray analysis and transcriptomic biomarkers. Together with Dr. Hare, she successfully developed a transcriptomic biomarker for the prediction of long-term clinical outcomes in patients with new onset heart failure and detection of myocarditis from a single endomyocardial biopsy. Furthermore, each biomarker revealed important targets for gene or cell therapy. For this work, she was awarded the Samual A. Levine Clinical Young Investigators Award from the American Heart Association, a grant from the Wallace H. Coulter Center and a fellowship of the Myocarditis Foundation. The novel biomarkers are currently validated in a clinical trial involving 150 patients, which will also be used to elucidate if blood cells can be used as a surrogate for heart biopsies (12;13).

Selected References

Chow LH, Radio SJ, Sears TD, McManus BM. Insensitivity of right ventricular endomyocardial biopsy in the diagnosis of myocarditis. J Am Coll Cardiol 1989; 14(4):915-920.

Hare J.M. The dilated, restrictive and infiltrative cardiomyopathies. In: Zipes DP, Libby P, Bonow R, Braunwald E, editors. Braunwald's Heart Disease. Elsevier, 2007.

Heymans S. Myocarditis and heart failure: need for better diagnostic, predictive, and therapeutic tools. Eur Heart J 2007; 28(11):1279-1280.

Barouch LA, Harrison RW, Skaf MW et al. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 2002; 416(6878):337-339.

Amado LC, Saliaris AP, Schuleri KH et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A 2005; 102(32):11474-11479.

Gonzalez DR, Beigi F, Treuer AV, Hare JM. Deficient ryanodine receptor S-nitrosylation increases sarcoplasmic reticulum calcium leak and arrhythmogenesis in cardiomyocytes. Proc Natl Acad Sci U S A 2007; 104(51):20612-20617.

Kittleson MM, Ye SQ, Irizarry RA et al. Identification of a gene expression profile that differentiates between ischemic and nonischemic cardiomyopathy. Circulation 2004; 110(22):3444-3451.

Heidecker B, Hare JM. The use of transcriptomic biomarkers for personalized medicine. Heart Fail Rev 2007; 12(1):1-11.

Kittleson MM, Ye SQ, Irizarry RA et al. Identification of a gene expression profile that differentiates between ischemic and nonischemic cardiomyopathy. Circulation 2004; 110(22):3444-3451.

Kittleson MM, Irizarry RA, Heidecker B, Hare J.M. Transcriptomics: Translation of Global Expression Analysis to Genomic Medicine. In: Willard H.F., Ginsburg G.S., editors. Handbook of Genomic Medicine. Elsevier, 2008.

Kittleson MM, Ye SQ, Irizarry RA et al. Identification of a gene expression profile that differentiates between ischemic and nonischemic cardiomyopathy. Circulation 2004; 110(22):3444-3451.

Deng MC, Eisen HJ, Mehra MR et al. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant 2006; 6(1):150-160.

Liew CC, Ma J, Tang HC, Zheng R, Dempsey AA. The peripheral blood transcriptome dynamically reflects system wide biology: a potential diagnostic tool. J Lab Clin Med 2006; 147(3):126-132.