Intracellular targeting Hsp70 for myocardial cytoprotection after an infarction

DESCRIPTION (provided by applicant): Heart disease statistics compiled by the American Heart Association in 2010 estimate 785,000 Americans, each year, will have a new coronary attack, another 470,000 will have a recurrent heart attack, and 195,000 will have a silent infarction, resulting in a coronary event every 25 seconds in the US. Myocardial cells affected by the infarction must endure hypoxic stress during the ischemic event and oxidative stress during reperfusion. Two decades of research suggests theinduction of a heat-shock protein 70 (Hsp72) in myocardial cells counteracts these stresses and improves post-ischemic contractile recovery. To date, clinically relevant methods of inducing Hsp70 in these cells have yet to be devised. We developed the Fvfragment of a cell- penetrating antibody, mAb 3E10, as an intracellular transporter to deliver the Hsp70 into cells, and we have demonstrated cytoprotection against oxidative damage in vitro and in vivo. The objective here is to establish proof-of-pri