A New Use of Clenbuterol in Treating Congestive Heart Failure (CHF)

Columbia Technology Ventures
posted on 10/22/2008

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*Problem or Unmet Need* Congestive Heart Failure (CHF), a progressive pathophysiologic condition, affects nearly 5 million people in the United States and is the only major cardiovascular disorder on the rise. Current drug treatment for heart failure primarily includes diuretics, ACE inhibitors, digoxin (also called digitalis), and beta- blockers. Typical doses of ACE inhibitors may cause numerous side effects, including decreased blood pressure, renal insufficiency, and potassium retention. With a growing population affected by heart failure, and current treatments not optimized to prevent side effects, there is a need for new and better methods for prevention and treatment of 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 either independently 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.

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.

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