Lead Inventors: Simon Maybaum, Jie Wang STV Reference: IR# 1675 & IR# 1509 Problem or Unmet Need: Heart failure, also called Congestive Heart Failure (CHF) is a progressive pathophysiologic condition where cardiac function is impaired to a degree that...

Lead Inventors: Simon Maybaum, Jie Wang STV Reference: IR# 1675 & IR# 1509 Problem or Unmet Need: Heart failure, also called Congestive Heart Failure (CHF) is a progressive pathophysiologic condition where cardiac function is impaired to a degree that the heart is unable to generate output sufficient to meet the metabolic requirements of the tissues and organs of the body. As a result, myocardial workload increases and may lead to further ventricular dysfunction and heart failure. In the United States heart failure affects nearly 5 million people and is the only major cardiovascular disorder on the rise. Current drug treatment for heart failure primarily involves diuretics, ACE inhibitors, digoxin (also called digitalis), and beta- blockers. In mild cases, thiazide diuretics, such as hydrochlorothiazide or chlorothiazide are useful. Typical doses of ACE inhibitors may cause numerous side effects, including decreased blood pressure, renal insufficiency, potassium retention, and coughing. Other methods of heart failure management include the recognition and control of factors that may be causing increased cardiac demands or adversely affecting myocardial function (e.g., hypertension, anemia, excess salt intake, excess alcohol, arrhythmias, thyrotoxicosis, fever, increased ambient temperature, or pulmonary emboli). However, these treat heart failure only indirectly. Accordingly, there currently exists a need for new and better methods for improving the survival of patient with heart failure. Details of the Invention: The invention establishes that adrenergic beta-2 agonists such as clenbuterol can be used to prevent and treat heart failure patients either alone or in combination with an adrenergic beta-1 antagonist such as metoprolol. Clenbuterol is a long-acting beta 2-adrenergic agonist approved for use in the treatment of pulmonary disorders in Europe. Oral clenbuterol has been also used extensively by athletes to enhance muscle size and strength. This new therapy will provide a unique strategy to reverse the remodeling of the left ventricle during heart failure and after myocardial infarction (heart attack). Clenbuterol and metoprolol target heart failure via different mechanisms and therefore produce synergistic effects. Metoprolol blocks beta-1 receptors and corrects neurohormonal imbalance, while clenbuterol stimulates beta-2 receptors and rescues myocytes, is anti-apoptotic, and improves the function of calcium-handling proteins. Applications: • Treats or prevents heart failure by treating or preventing heart tissue degeneration or reversing the effects of heart failure through the normalization of calcium homeostasis. The heart failure degeneration can be ischemic or non-ischemic and in an acute or chronic condition. It may also result from myocardial infraction. • Prevents heart failure in a subject with a pre-heart failure condition. Advantages: • Improves patient quality of life • Lessens symptoms of heart failure, including shortness of breath or fatigue • Decreasing hospitalizations for exacerbations of CHF • Improves survival for patients with CHF • Clenbuterol improves muscle strength and cardiac function in patients with CHF not supported by a left ventricle assist devices (LVAD) • In a model of chronic, ischemic heart failure, clenbuterol treatment led to clear improvements in calcium homeostasis, diastolic function, myocardial apoptosis and DNA repair Patent Status: Patent Pending (WO/2005/037230) Licensing Status: Available for Licensing and Sponsored Research Support

Pat. Title: CLENBUTEROL FOR CHF Methods for treating and preventing heart failure Compositions and Methods for Treating Heart Failure Novel use of clenbuterol for treatment of congestive heart failure Novel use of clenbuterol for treatment of congestive heart failure

Publication #: WO 2005/037230 was Cohen Tauber

App. #: 60/549,803 60/549,803 US04/034426 60/511,619 60/511,619

Licensing or sponsored research support