Early Translational I
ICOC Funds Committed:
The goal of this project is to develop a cell-based treatment for heart disease that will increase blood flow to the heart and repair damaged heart tissue by directly adding new cardiac cells to the heart muscle wall. This therapy is intended to restore the pumping function of the heart and reverse the symptoms of Heart Failure by treating the underlying causes of the disease. Our proposed technology is based upon two existing components, each of which contains a different population of human cells. The first component is an engineered human tissue patch that is FDA-approved for wound healing and is currently being evaluated in human clinical trials in the United States for the treatment of heart disease. Formation of new mature blood vessels and healing of damaged and ischemic tissues in response to the patch has been demonstrated in animals and humans. The second component is a highly purified population of FDA-compliant human embryonic stem cell-derived cardiac progenitor cells generated in a certified GMP facility. These cardiac progenitor cells can form beating cardiac tissue in vitro when permitted to mature, and are capable of replacing lost or damaged heart muscle. We plan to test whether these cells are also capable of integrating with a patient’s cardiac tissue after implantation, and whether this can improve global heart function. We will evaluate whether the combination of the tissue patch and the cardiac progenitor cells can address certain limitations of cardiac cell therapy. If successful, we hope to demonstrate several advantages. First, that the tissue patch may provide a means for reliable and reproducible delivery of these “myocardial replacement” cells to the heart. Second, that delivery via a patch can enhance survival of these cells in a patient’s damaged heart tissue, as well as promote successful engraftment into the heart. Third, that better control over the delivery of the cardiac progenitor cells may be achieved using a patch methodology versus infusion or injection, which could reduce or eliminate ectopic node formation. And finally, that establishment of a viable culture of cardiac progenitor cells in the patch prior to implantation could allow a controlled dose of these cells to be delivered to the heart in a site-specific manner. Successful completion of this project will advance our proposed therapeutic technology to IND-enabling pre-clinical studies in three years.
Statement of Benefit to California:
In the United States, Heart Failure (HF) results in more deaths than cancer, accidents, and strokes combined, costing more than $35 billion annually. It is estimated that in the United States, 5,300,000 patients have HF, with an additional 550,000 new cases per year. Cardiovascular disease is the leading cause of death in California where there are annually about 575,000 heart disease-related hospital discharges and 350,000 of these are for HF. The vast majority of patients who develop Heart Failure in the US do so after myocardial infarction (MI). According to the American Heart Association, approximately 22 percent of male and 46 percent of female MI victims will be disabled with HF within six years. The annual incidence of MI in the United States is 600,000 for first a first attack and 320,000 for recurrent attacks. Once a patient becomes symptomatic with HF, the prognosis is worse than many forms of cancer. A patient with symptomatic HF has a mortality rate approaching 50% in five years. HF is a progressive disease, which ultimately leads to death. Current therapies temporarily relieve symptoms, but there is no cure. The only treatment for the most advanced cases is a heart transplant, which is not a feasible option for most patients. The need for donor organs for the sickest patients far exceeds the number available. Cell replacement therapy is a more practical alternative, but there is currently an insufficient supply of appropriate cells for cardiac muscle replacement. Human embryonic stem cells can address this need, as they are unlimited in proliferative capacity and are capable of differentiating into cardiac cells for heart muscle repair. New therapeutics targeting the progression of HF will make a significant economic impact in the United States and in California. Successful development of a therapeutic that can treat or reverse Heart Failure will result in cost reductions in the care of cardiovascular disease, and an increase in productivity and quality of life for a large sector of the population. We hope to demonstrate that our proposed cell-therapy product will halt the progression of HF or even reverse the deleterious effects of HF on the patient's heart. By restoring the pumping ability of the heart, this product, if successful, will help the HF patient to lead a more normal, active life. Successful development of this product will contribute to the broader goal of advancing stem cell-derived therapeutics through the clinical and regulatory process and will help pave the way for other stem cell-derived therapies to improve public health.