Short peptides useful for treatment of ischemia/reperfusion injury and other nitric oxide associated tissue damage
Professor of Biochemistry
Background and Description of Technology:
In the US alone, over one million individuals suffer a myocardial infarction annually. When victims are rushed to a hospital, blood flow is restored (the process known as reperfusion) either by drugs that dissolve clots or by angioplasty. Tissue salvage, however, is severely limited by free radicals and inflammatory responses, which cause as much as 80% of the damage during reperfusion (ischemia-reperfusion (I/R) injury). A primary outcome of damage resulting from I/R injury is chronic congestive heart failure. 12% of patients die within three months of diagnosis, 33% die within one year, and 60% die within five years. Apart from accidental heart attacks, I/R injury is also a common outcome in cardiac surgery, leading to a spectrum of damage including arrhythmias, post-ischemic myocardial dysfunction, and cardiogenic shock. Furthermore, I/R injury is not limited to heart muscle, and also frequently occurs in the brain (stroke), liver, skeletal muscles and other organs.
Dr. Nudler has developed a group of tetrapeptides rationally designed to denitrate proteins and, in doing so, reversing tissue damage associated with excess nitric oxide (NO) and its reactive species. These active tetrapeptides, and their analogues, are characterized by a unique combination of stacking, ionic and hydrophobic interactions that allow them to efficiently transfer the NO2 group from tyrosine to its thiol group. In rat models (acute and 30-day models) of myocardial infarction, tetrapeptide produced a significant diminution in infarct size and preservation of numerous hemodynamic functions, including left ventricular function. These results were collected four weeks after the ischemic insult. Most significantly, since these peptides can repair as well as prevent I/R damage, they can be administered subsequent to an event.
Patent applications have been filed and NYU is seeking commercial partners to develop tetrapeptide-related therapeutics targeting conditions that result form tissue damage associated with excess NO and its reactive species including: I/R injury of heart muscle associated with heart attack or cardiac surgery, I/R injury of brain tissue associated with stroke, I/R injury of liver tissue, skeletal muscles, etc., various autoimmune and inflammatory diseases.