Disease Team Therapy Planning I
Despite advances in medical and surgical therapies, heart disease remains a major cause of morbidity and mortality. There are an increasing number of patients with significant morbidity despite optimal medical management. Heart transplantation is an established treatment for end-stage congestive heart failure. Yet, this definitive therapy is limited to only 2000 donor hearts per year, creating a major public health concern and a significant clinical problem. The existing therapies for end-stage cardiac failure (LVAD implantation and transplantation) carry not only major emotional and fiscal costs but are limited by the supply of hearts and by issues related to rejection. Researchers are studying whether cellular therapy may be capable of repairing a diseased heart. Numerous clinical trials have demonstrated favorable effects toward the use of autologous stem cells in AMI patients with considerably low side effects. However, clinical studies suggest that adult stem cell therapy provides only limited efficacy. The problem with auto-transplantation in patients with heart failure is intrinsically associated with the age of the patients: majority of patients are old and their own adult stem and satellite cells may have decreased regenerative and immuno-modulatory potential. The objective of this proposal and our International Team is to develop IND-enabling studies (i.e. toxicology, analytical assay development, process development and manufacturing, clinical and regulatory strategy development) for a combination product made up of a bio-scaffold imbedded with patient-specific adult stem cells, genetically manipulated to expand their regeneration potential and prevent and/or repair abnormalities associated with age of patient. Our approach is grounded in fundamental investigations performed by the team members and our Established Team has a distinguished history of success. Fabricated bio-scaffolds that match the exact biomechanical and biophysical requirements of the implanted tissue are already in pre-clinical test in a large (pigs) and small animal models in coordination with the work of a European consortium funded by the European Commission (7 Frame Program Grant, RECATABI). Our team will integrate and synergize their capacities in order to manufacture and fully characterize a novel clinical platform to regenerate necrotic ischemic tissues after AMI for patients with end-stage congestive heart failure (CHF) with a simple one-time “smart-patch” technology application.
Statement of Benefit to California:
Heart failure is the end-stage of many cardiovascular diseases and its leading cause is the presence of a large scar due to acute myocardial infarction (AMI). The economic implications of AMI are enormous. Over 17% of all medical expenditures, or $149 billion annually, and nearly 30% of Medicare expenditures were attributable to this disease in 2007. The total medical bill for Americans with heart disease is expected to triple in the next two decades, increasing to $818 billion in 2030 as the population ages. The large number of people with cardiovascular disease who are eligible for both Medicare and Medicaid could lead to large shifts in the burden to these social insurance programs as prescription drug coverage is included in the Medicare coverage. After more then a decade of discovery, stem cell therapy has progressed significantly in the area of understanding and direct application of stem cells. Our proposal is aimed to optimize and standardize a production of combination autologous product. It will provide sufficient preclinical data to establish a scientific rationale for clinical investigation and to demonstrate an acceptable safety profile of the novel product and its delivery system. This research will pave the way for the development of safe clinical applications prior to initiating a clinical trial. It’s aimed to meet regulatory requirements and milestones in developing cellular therapies for the treatment of cardiac disease, with recommendations on the design of preclinical and clinical studies, and on the chemistry, manufacturing, and controls (CMC) information in accordance with FDA guidelines avoiding unintended side-effects and additional costs related to its correction. Our Disease Planning Initiative will utilize the expertise and innovations of European Consortia funded by the European Commission (7 Frame Program Grant, RECATABI), transforming their knowledge, utilizing Consortia reagents as well as professionals expertise to complement and further expand California Based Investigations performed at Buck Institute for Research on Aging and clinical facility of UCSD. While developing human autologous cell-based therapies in California, our proposed program therefore significantly increases the options available in the California health care system. IND-enabling product, in planning stage of development, is expected to reduce the long-term health care costs to California by providing cures to a disease that currently requires an expensive periodic treatment. Our research is also expected to stimulate the development of biotechnology industry focused on clinical applications of autologous stem cells. Such development will be of great benefit to California by attracting high-skilled jobs and tax revenues, and by making the State a leader in a field that is poised to be the economic engine of the future. The State of California will also stand to benefit from the intellectual property generated by this research.