An estimated 16.3 million Americans suffer from coronary heart disease. Every 25 seconds, someone has a coronary event and every minute, someone dies from one. Treatment for coronary heart disease has improved greatly in recent years, yet 1 in 6 deaths in the US in 2007 was still caused by this terrible disease. Stem cells have been used as an supplemental form of treatment but they have been most effective for patients treated immediately after their first heart attack. Unfortunately, stem cell therapy for chronic heart disease and heart failure has been less successful. With current delivery methods for stem cells into the heart, most are washed away quickly, whereas our device will hold them in the area that needs repair. With this project we are testing a novel approach to improve the benefits of stem cell therapy for patients suffering from chronic heart disease. By applying a type of bone marrow stem cells known to enhance tissue repair (mesenchymal stem cells) to a biological scaffold, we hope to greatly amplify the beneficial properties of both the stem cells and the biological scaffold. This device will be implanted onto an appropriate preclinical model that have been treated so as to mirror the chronic heart disease seen in humans. We predict that this novel device will heal the damaged heart and improve its function to pave the way for a superior treatment option for the thousands of Americans for whom the unlikely prospect of a heart transplant is currently the only hope.
Heart disease is the number one cause of death and disability in California and in the US as a whole. An estimated 16.3 million Americans over the age of 20 suffer from coronary heart disease (CHD) with an estimated associated cost of $177.5 billion and CHD accounted for 1 in 6 deaths in the US in 2007. Advances in treatment have decreased early mortality but consequently lead to an increase in the incidences of heart failure (HF). Patients with HF have a 50 percent readmission rate within six months, which is a heavy cost both in terms of quality of life and finances. The high cost of caring for patients with HF results primarily from frequent hospital readmissions for exacerbations. The need for efficient treatment strategies that address the underlying cause, massive loss of functional myocardium, is yet to be met. We believe that present project proposal, development of a combined mesenchymal stem cell and extra cellular matrix scaffold device, will lead to improved standards of care for patients suffering from chronic myocardial infarction who are thus at risk of developing HF. By not only retarding disease progression but by actually restoring cardiac function, we believe that the proposed project will have a tremendous impact on both the cost of care as well as the quality of life for large groups of Californians and patients worldwide for whom the improbable prospect of heart transplantation is the only curative treatment option available.
This development candidate (DC) proposal aims to evaluate the potential of allogeneic bone marrow derived mesenchymal stem cells (MSC) seeded onto an FDA-approved biological scaffold as a therapy for the treatment of chronic myocardial infarction. The applicants hypothesize that the combination of the scaffold and MSCs will improve engraftment and enhance the therapeutic impact, compared to either element alone. They plan to develop and characterize the cell-scaffold device in vitro, and then perform in vivo testing to ensure safety after transplantation. In parallel, the team will optimize a relevant preclinical model of chronic myocardial infarction. Next, the applicants will test their cell-scaffold combination in the model for the ability to significantly improve cardiac function over cells or matrix alone.
Objective and Milestones
- The panel commended the applicants’ clearly defined objective to achieve a DC.
- Reviewers found the target product profile appropriately developed and noted that the applicants identified an appropriate patient population.
- The applicants presented appropriate milestones and success criteria to evaluate the program’s progress.
Rationale and Significance
- The group appreciated the compelling unmet medical need faced by patients with chronic infarcts.
- The choice of MSC for the development candidate was debated by the panel, since many investigators have studied MSC in this indication and the data in this field are contradictory regarding durable functional benefit.
Research Project Feasibility and Design
- The application lacked compelling preliminary data to support the core hypothesis that the proposed cell-scaffold device would increase cell retention and enhance tissue regeneration better than either cells or scaffold alone in the target indication. Reviewers noted this as a weakness and found the application premature for a DC award.
- The panel did not find the proposed DC particularly novel. A discussant noted that previous preclinical and clinical attempts to retain MSC at the delivery site have not convincingly demonstrated improved heart function.
Qualification of the PI (Co-PI and Partner PI, if applicable) and Research Team
- The Principal Investigator (PI) and well-assembled team possess the necessary skills and translational experience to successfully execute the proposed program.
- The PI has direct experience with use of the proposed biomaterial and a co-investigator brings experience with the cell component of the project.
- The application lacks letters of support from co-investigators as well as a communication and coordination plan for the large team, increasing the risk of the project.
Collaborations, Assets, Resources and Environment
- Facilities and assets available to the team are excellent.
Responsiveness to the RFA
- The proposed program is responsive to the RFA.
- This application scored below the initial scientific merit funding line, no programmatic reason to fund the application was proposed, and the GWG voted to place the application in Tier 3, Not Recommended for Funding.