Nitric oxide is important in maintaining electrical stability of the heart. In heart failure and/or other states of cardiac injury, neuronal nitric oxide synthase (NOS1) levels within the heart rise and NOS1 translocates from the sarcoplasmic reticulum (SR) to the plasma membrane. As this phenomenon could have either deleterious effects or adaptive consequences, it is imperative to definitively address the issues of the physiologic role of NOS1 in the heart as NOS1 deficiency may lead to both depressed myocardial contractility as well as to sudden cardiac death.
Solution
Identification of agents or drugs which modulate the levels of nitric oxide in the heart. One such agent would be a nitric oxide (NO) donor or functional nitric oxide synthase molecule in a pharmaceutical composition. The agent functions by modulating the ryanodine receptor (RyR) S-nitrosylation to normal levels as compared to a normal subject.
Competitive Advantage
Understanding the mechanisms related to nitric oxide synthase, are important in the development of agents that would effectively and rapidly treat a person undergoing a heart attack. Just as significant would be the ability to modulate the nitric oxide levels in patients at risk for heart attacks, thus prophylactically treating these populations and saving lives, productivity and healthcare costs.
Applications
1) Treating patients with cardiac diseases and disorders, especially those suffering from a heart attack.
2) Diagnosis of patients by screening for levels of nitric oxide synthase.
3) Screening genetic differences in nitric oxide synthase nucleic acids, expression of nitric oxide synthase proteins and peptides provides for the diagnosis of various heart diseases or disorders, especially those at risk of a heart attack.
Patent Status
International patent application WO2009059271 entitled, "DIAGNOSIS AND TREATMENT OF CARDIAC DISORDERS," was published on May 7, 2009.
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. Over many years, Dr. Hare and his laboratory put one of their major focuses on transcriptomic biomarker research, 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.
Dr. Daniel Gonzalez is a post-doctoral fellow at Intersidisciplinary Stem Cell Institute. Trained in the Pontificia Universidad Catolica in Santiago, Chile and in Johns Hopkins, Baltimore, his research has focused in the role of nitric oxide in the heart in health and disease.
Selected References
Barouch LA, Harrison RW, Skaf MW et al. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 2002 March 21;416(6878):337-9.
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 August 9;102(32):11474-9.
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 December 18;104(51):20612-7.
Kittleson MM, Ye SQ, Irizarry RA et al. Identification of a gene expression profile that differentiates between ischemic and nonischemic cardiomyopathy. Circulation 2004 November 30;110(22):3444-51.
Hare J.M. The dilated, restrictive and infiltrative cardiomyopathies. In: Zipes DP, Libby P, Bonow R, Braunwald E, editors. Braunwald's Heart Disease. 8 ed. Elsevier; 2007.
Gonzalez DR, Fernandez IC, Ordenes PP, Treuer AV, Eller G, & Boric MP (2008). Differential role of S-nitrosylation and the NO-cGMP-PKG pathway in cardiac contractility. Nitric Oxide 18, 157-167.
