The proposed research will set out to demonstrate the safety and feasibility, in patients, of a novel treatment for heart failure based on heart-derived stem cells. The focus is on patients who have been diagnosed with a form of heart failure known as dilated cardiomyopathy (DCM). Currently, DCM is the most common type of heart failure, a disease which affects ~5 million Americans and which is one of the major causes of death and disability; it generally results from coronary atherosclerosis and multiple MIs, but can also be idiopathic in nature. The timing and course of the disease differs between individuals but ultimately the progression of disease leads to chronic heart failure. Medication and mechanical devices can be effective in slowing the progression of heart failure, but there is no known commercial therapy that can reverse the progression of the disease process. The heart remodels (i.e., dilates) to offset the loss of functional heart muscle. The remodeling process is ultimately maladaptive, with profound changes in cardiac structure and function as well as in the underlying molecular and cellular pathways. Conventional therapy relies largely on drugs that block secondary maladaptive signaling pathways; they slow the progression of heart failure, but do not reverse the disease. Once DCM becomes symptomatic, with shortness of breath and limited exercise capacity despite best current therapy, clinical outcomes are dismal. The one-year risk of death or hospitalization in such patients approximates 40%. Cell therapy has the potential to achieve myocardial regeneration and thus to improve, qualitatively, the prospects of these desperately ill patients.
We will perform the DYNAMIC Phase 1 trial of allogeneic cardiosphere-derived cells in patients with DCM. DYNAMIC will study 42 patients (14 controls and 28 cell-treated). Functional testing will include cardiac imaging by echo and PET/CT in order to gain extensive information about perfusion, structure and function and how they may respond to therapy. Clinical events data will also be collected so as to better power follow-on studies seeking to reduce death and hospitalization.
By the end of the project, we expect to have completed a clinical trial of a promising form of cell therapy in a highly-deserving patient population. The data collected will be vital in planning more advanced clinical studies that will determine, definitively, whether the treatment saves lives.
Statement of Benefit to California:
Cardiomyopathy is a group of heart-related diseases that affects heart muscle. This research focuses on dilated cardiomyopathy, which is the most common form and is typically characterized by the progressive, usually irreversible enlargement of heart muscle. Dilated cardiomyopathy is common, accounting for more than half of the ~5 million cases of heart failure in the USA today. Currently, the only treatment for dilated cardiomyopathy is management through optimal medication and lifestyle changes. Management of the disease focuses on reducing the symptoms and slowing disease progression. There is no known cure for dilated cardiomyopathy nor has there been a proven strategy to stop its progression, or to reverse established disease. This research is aimed at using heart-derived cell therapy, the only known intervention, to date, that has been proven clinically effective in regenerating the human heart. If our research is successful, we may offer a cost-effective way to reduce the tremendous damage to Californians inflicted by this type of heart disease. This in turn may also reduce the economic burden presently borne by taxpayers who support the health care systems in California. In addition to the public health benefits, spinoff technology developed by this disease team will benefit existing California-based biotechnology companies, leading to fuller employment and an enhanced tax base.