Autologous Delivery of Pim-1 Enhanced Cardiac Stem Cells: A Novel Clinical Therapy for Cardiac Muscle Regeneration Post MI

Funding Type: 
Disease Team Research I
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

There have been consistent advancements in the prevention and treatment of cardiovascular disease. Despite these advancements and partly due to the increasing age of the human population, heart attacks continue to be a human plague currently affecting 5 million people. Heart attack is the most common cause of hospital admission leading to 300,000 deaths each year in the US. The average 5-year survival for these patients is only 50%. The most aggressive treatment for these patients is heart transplantation but this is limited to only 2,000 patients each year because of a serious lack of suitable donors. Therefore, there is an urgent need for new ways to treat patients suffering from heart failure.

In the last 10 years, much work has been done on the use of stem cell therapy for organ failure. Recent reports indicate some successes using stem cell therapies to treat heart attack but only limited, short-term benefit has been seen. {REDACTED} has discovered a new type of stem cell therapy for heart attack. This technique uses stem cells taken from the patient’s own heart. The cells, called adult human cardiac progenitor cells (hCPCs), are modified to produce a protein (Pim-1) known to protect the heart and also found to protect hCPCs after they are returned to the patient’s heart. Animal data shows that Pim-1 modified hCPCs are able to generate new heart tissue that persists for at least 6 months and causes major improvements in the heart’s ability to work. In this proposal, the {REDACTED} will partner with {REDACTED} and his colleagues at {REDACTED}, who are recognized experts in tracking fate of stem cells. They will validate survival of Pim-1 modified hCPCS in small and large animal models using state-of-the-art molecular imaging technologies. The third member of the disease team is {REDACTED}. {REDACTED} exists specifically to advance the Pim-1 technology to the point of evaluation by the Food and Drug Administration (FDA) for potential use in human patients. We anticipate that the work conducted in this proposal will result in an application to FDA for the first human clinical trial using the patient’s own hCPCs, modified to produce Pim-1, as a therapy for heart attack and prevention of subsequent heart failure through the generation of new heart muscle.

Funding of this proposal will: 1) Develop procedures for Pim-1 modification in hCPCs, 2) Develop quality-assured procedures and perform clinical quality manufacturing of Pim-1 modified hCPCs, 3) Demonstrate safety and efficacy of these modified hCPCs under quality-assured pre-clinical conditions in large animal models, 4) Design the human clinical trial protocol and related documentation that will be proposed to FDA, 5) Compile all documents required for the submission of the Investigational New Drug Application (IND) to FDA, and 6) Submit the IND to FDA by the end of year 4 of this proposal.

Statement of Benefit to California: 

In 2004, the total healthcare cost in the US was 1.9 trillion dollars and cardiovascular disease ranked as the most costly disease category, accounting for 8.3% of these overall costs. Cardiovascular disease and, in particular, myocardial infarction resulting in congestive heart failure, continues to be the number one cause of death in the US, killing some 300,000 Americans each year. Congestive heart failure is also the leading cause of hospital admissions. There are nearly 5 million Americans who are suffering from this illness, with 550,000 new cases reported annually. Despite recent advances in drug therapies for acute myocardial infarction, the average five-year survival for patients suffering this condition remains only at roughly 50% level. While cardiac transplantation is a well-established treatment for end-stage congestive heart failure, this treatment is limited to only 2,000 patients per year due to a severe and chronic shortage of acceptable donor hearts. As the most populous state, California bears the greatest public health impact of myocardial infarction and congestive heart failure as well, a burden that is only getting heavier as the population ages. Thus, there is a clear need for development of novel therapies for these disease conditions, the development of which will benefit California tremendously, from its population to the state’s public health system and its foundation in biomedical research. One such cutting edge treatment uses the Pim-1 modified cardiac progenitor cell (CPC) technology developed by investigators at {REDACTED}, which has already shown significant promise in relevant animal models of ischemic heart disease.

In addition to the cost saving benefits that will be realized by the California healthcare system as a result of the development of this technology, there will also be significant economic development benefits realized by the State. Although biotechnology is a robust business sector in California, this sector is currently suffering from the economic downturn as venture funding dries up and jobs are being lost. Funding of this proposal will directly support existing jobs within California’s biotechnology industry at the firms designated for the development work. All the funds specifically targeting scientific procedures will be reinvested in California, fueling economic growth and recovery in addition to furthering a likely revolutionary treatment of heart failure. This funding will also serve to create new jobs at {REDACTED} and other companies associated with the Pim-1 modified hCPC technology. Synergy can result as other cell therapies using related technologies and targeting other disease areas are likely to develop as a consequence of this funding. These funds will also directly support education and jobs at {REDACTED} coping with painful budget reductions resulting in loss of critical talent and research momentum.