Cardiovascular disease is the leading cause of mortality and morbidity in the United States and is predicted to be a leading cause of death worldwide. Each year, over 19 million incidents of sudden cardiac events occur worldwide, with approximately 1 million of those in the United States. Despite the advances in medical treatment and interventional procedures to reduce mortality in patients with acute coronary syndrome, the number of patients with refractory myocardial ischemia and congestive heart failure is rapidly increasing. Currently, heart transplantation is the only successful treatment for end-stage heart failure; however, the ability to provide this treatment is limited by the availability of donor hearts. There is an urgent need to develop alternative therapies for both acute myocardial infarction and chronic cardiomyopathies.
Recent work indicates that stem cells delivered via direct intramyocardial injection or intracoronary injection following acute MI have produced mixed results showing improvement of LV function of injured myocardium in humans with one study demonstrating sustained benefit; but other studies producing negative trials or transient benefit. The reasons for failure to translate preclinical results into benefits in humans are not known, but a good candidate is the vast difference in cell number required for human therapy compared to rodents. Additionally, advocates recognize major limitations due to lack of specific means to deliver the cells efficiently and effectively.
Human antibodies for identification, selection and specific delivery of therapeutic stem cells will be developed. The identification and isolation of a specific human embryonic stem cell derived heart muscle antibodies would be a significant milestone since there presently are no human specific antibodies for human embryonic stem cell derived heart muscle. The isolation of antibodies will be a technical advancement to allow for the identification and potentially lead to selection techniques which will overcome one of the major hurdles of human embryonic stem cell derived heart muscle which is obtaining adequate numbers to be transplanted. The development of an antibody technology that will deliver the stem cells specifically to the area of a heart attach and/or beneficially influence the local tissue environment will enhance the field of myocardial regeneration. The developed technology can be potentially adapted to other organs as a tool for tissue regeneration.
Statement of Benefit to California:
The funding from the CIRM grant will lead to critical proof of concept studies regarding the utility of our “targeting” technology for stem cells in myocardial repair. Cardiovascular disease is the leading cause of mortality and morbidity in California and the United States. Myocardial infarctions are also a leading cause of premature, permanent disability in the labor force, accounting for 19 percent of disability allowances by the Social Security Administration. Therapies directed at preventing and treating congestive heart failure resulting from myocardial infarctions would help reduce the social and economic impact from lost wages as well as reducing costs to the healthcare system.
The benefit to the California economy will arise from the ongoing product development. The technology being developed creates a new line of tools for regenerative medicine. The technology builds and expands on the biotechnology sector and will lead to products used clinically to initially treat cardiovascular patients. Additionally, the technology being developed can be used for stem cell isolation and separation kits.
The optimization of the antibodies would lead to the creation of new jobs within California. The commercialization of the antibody targeted stem cell therapy could potentially lead to a new industry within California. As part of the process of developing a therapeutic product, jobs will be created at academic centers and the private sector to demonstrate proof of concept studies as well as regulatory, preclinical testing, manufacturing, sales and clinical trials.