Multifunctional antibody therapy for acute myocardial infarction Patients with acute coronary syndrome (ACS) suffer from a range of acute myocardial ischemic states. Thrombolysis and percutaneous intervention (PCI) are used to reperfuse the ischemic tissue and stabilize damage caused by infarction. After acute myocardial infarction (AMI), ischemic tissues undergo cell death from necrosis and apoptosis, followed by inflammation and a process of granulation leading to scar tissue formation. The goal of this project is to minimize the level of cell death that occurs immediately after reperfusion and to rapidly restore damaged vasculature and myocardium by establishing a regenerative extracellular matrix (ECM) environment and chemotactic signals necessary for recruitment and differentiation of endogenous stem/progenitor cells. This approach combines multiple functional domains proven to act independently, that are specifically delivered to ischemic myocardium by antibody targeting. This approach has several advantages, including intravenous delivery of a protein therapeutic, and the ability to dose both immediately after reperfusion as well as periodically thereafter to maintain therapeutic efficacy over the course of recovery. Success in phase 1 of the project will identify a clinical candidate for further development. Phase 2 will focus on the production of clinical grade material and preclinical studies to support filing of an IND for a clinical trial in patients with acute myocardial infarction
Project Terms: Accounting; Acute; acute coronary syndrome; Acute myocardial infarction; Affect; angiogenesis; Animal Model; Anoikis; Antibodies; Antibody Therapy; Apoptosis; Autophagocytosis; Binding; Biochemical; Biodistribution; Cardiac Myocytes; Cardiovascular Diseases; Cell Death; Cessation of life; chemical conjugate; Chimeric Proteins; Cicatrix; Clinical; clinical candidate; clinical development; Clinical Trials; Collagen Type IV; critical period; CXCR4 gene; Cytoplasmic Granules; Developed Countries; Developing Countries; Development; Dose; Engineering; Environment; Extracellular Matrix; Fibronectins; Germ Cells; Goals; Heart; Heart Arrest; Heart failure; heart function; Heart Transplantation; Hour; improved; In Vitro; Induction of Apoptosis; Infarction; Inflammation; Infusion procedures; Injections; injured; Intervention; Intravenous; Ischemia; Mammalian Cell; Matrix Metalloproteinases; Mediating; Methods; Morbidity - disease rate; mortality; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardium; Myosin ATPase; Natural regeneration; Necrosis; novel; Patients; Peptide antibodies; Peptide Hydrolases; Peptides; Phase; preclinical study; prevent; Process; Production; progenitor; Property; Proteins; Quality of life; Recombinant Antibody; Recovery; recruit; regenerative; Reperfusion Therapy; Resistance; response; Rodent Model; Severities; SH2D1A gene; Signal Transduction; Site; stable cell line; stem; stem cell population; stem cell therapy; Stem cells; Stromal Cell-Derived Factor 1; success; Surface; Therapeutic; therapeutic protein; thrombolysis; Time; tissue repair; Tissues; Toxic effect; Transfection; Treatment Efficacy; trend; United States; Vascularization; Ventricular Function; Ventricular Remodeling;
