Myocardial Infarction Therapeutics

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R43HL097464-01
Agency Tracking Number: HL097464
Amount: $199,085.00
Phase: Phase I
Program: SBIR
Awards Year: 2009
Solicitation Year: 2009
Solicitation Topic Code: N/A
Solicitation Number: PHS2009-2
Small Business Information
DUNS: 828763263
HUBZone Owned: Y
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (603) 650-3903
Business Contact
Phone: (617) 320-8521
Research Institution
DESCRIPTION (provided by applicant): Myocardial infarction (MI) is the leading cause of death in the developed world, including the United States. Each year over 8.1 million Americans have an MI; 30% die before reaching hospital and 10% die after hospitalization. The goal of these studies is to advance a novel therapeutic approach to MI wound healing that is both strikingly effective and exactly contrary to conventional wisdom in order to help the 70% of MI victims that reach hospital. Temporary depletion of dendritic cells (DC) during MI wound healing results in a 49% improvement in cardiac function and a 65% reduction in MI size in a murine model. Cardiac function is the greatest determinant of survival post-MI, and also has a significant effect on quality of life. The goal of this project is to begin to develop this seminal discovery into a therapy for humans. The drugs to be evaluated are antibody-toxin conjugates designed to deplete DC post-MI. Their observed effect on MI wound healing is noteworthy for at least two reasons. First, immunologists and cardiologists have conventionally thought that interfering with wound healing through the depletion of DC post-MI would result in catastrophe: i.e. weakened tissues (cardiac rupture) and no new vasculature. This has not been the case. Second, the beneficial effect of DC depletion is startling in its magnitude (49% improvement in heart function). In Phase I, we will study two transgenic mouse models which express human receptors (DEC 205 and mannose) on their DC to determine safety and efficacy of the two the human mAb conjugates which comprise our lead therapeutic candidates. Aim 1. is to determine efficacy of these drugs in the murine models. Aim 2. is to measure the toxicity, distribution and elimination of lead drug candidate identified in Aim 1. A treatment that temporarily depletes DC is nothing short of a paradigm shift. Initial results suggest that this strategy may lead to a sharp reduction in mortality and profound improvements in the lives of victims of MI. PUBLIC HEALTH RELEVANCE: Heart attacks are the leading cause of death in the developed world. By temporarily depleting a cell type commonly associated with inflammatory and immune responses, we have been able to dramatically improve heart function after a heart attack in mice. The overall goal of this project is to advance these results toward a drug that will help humans.

* Information listed above is at the time of submission. *

Agency Micro-sites

SBA logo
Department of Agriculture logo
Department of Commerce logo
Department of Defense logo
Department of Education logo
Department of Energy logo
Department of Health and Human Services logo
Department of Homeland Security logo
Department of Transportation logo
Environmental Protection Agency logo
National Aeronautics and Space Administration logo
National Science Foundation logo
US Flag An Official Website of the United States Government