Congestive Heart Failure (CHF)
Heart failure is a progressive disease that is defined as an in ability of the heart to provide adequate blood flow throughout the body due to damage of the heart tissue. When the heart is unable to keep up with the normal demands required to pump blood, remodeling occurs to compensate for the heart’s decreased function. Remodeling includes enlargement of the heart, increased muscle mass and wall thickening, and increased heart rate. Symptoms of heart failure include fluid collection in tissues and lungs, shortness of breath and fatigue. The causes of heart failure are varied and can include coronary heart disease, high blood pressure, diabetes, cardiomyopathy, heart valve disease, arrhythmias and congenital heart defects.
Currently, there is no cure for heart failure. According to the American Heart Association, heart failure affects 2% of the population and causes 300,000 deaths each year in the Unites States alone. In 2008, the estimated total cost of heart failure in the United States was $37.2 billion dollars.
Heart failure is a chronic and progressive disease that requires lifelong management. Treatments include pharmaceutical management, lifestyle changes and risk factor reduction. Medications include vasodilators such as ACE inhibitors and Angiotenson II receptor blockers, beta blockers to decrease heart rate and blood pressure, diuretics to prevent fluid buildup, and aldosterone antagonists to improve heart function. More severe cases required surgical procedures to prevent further tissue damage. However, many patients continue to worsen despite these interventions, and there is a high rate of mortality associated with the condition.
Given that heart failure is often caused by damage to the heart tissue due to reduced blood flow and oxygen supply, an increase in blood supply to the heart tissue would help prevent further tissue damage and progression of the disease. MultiStem has shown benefit in preclinical models of cardiovascular disease, demonstrating an ability to promote formation of new blood vessels, reduce local and systemic inflammatory activity and protect cells and tissue in the region of damage. We believe that multiple factors produced by the cells could provide benefit to heart failure patients, through improved blood flow and may assist in the reversal of remodeling. In addition, an “off the shelf” product may provide benefit for heart failure patients who may be too compromised to undergo an autologous bone marrow draw. Building on our experience in acute myocardial infarction, our strategic goal is to develop a clinical program to treat ischemic heart failure patients with MultiStem with the goal of improving heart function and clinical outcome.
Figure: Treatment with allogeneic MultiStem increased vessel density in the border region of the infarct zone in a rat model of heart failure at 4 weeks compared to control animals. Vessel density was determined by the number of VWF staining vessels (in green) per mm2.