Growth Factor Treatment of Myocardial Infarction
None of the existing treatments for myocardial infarction are as simple as an intravenous perfusion of netrin-1. Current intravenous drugs serve a primarily supportive role, and angioplasty is an invasive procedure.
Direct intravenous injection of netrin-1 into patients at the first sign of a cardiac event to reduce infarct size and myocardial injury.
The invention is the use of netrin-1 to reduce infact size during myocardial infarction events, and a method of administering netrin-1 to confer powerful cardioprotective effects. Netrin-1 is a secreted molecule that is largely known to play a role in guiding vertebrate commissural axons in neuronal development. It also has a critical role in endothelial cell proliferation, migration, and angiogenic signaling in addition to morphogenesis of epithelial cells. However, UCLA investigators have now demonstrated that the pre-perfusion of netrin-1 can also directly reduce infarct size and myocardial injury in an animal model. In fact, experimental evidence shows that netrin-1 pre-perfusion of mouse hearts reduced ischemia-reperfusion induced infarct size dramatically from 42.5% (±3.6%) to 21.8% (±4.9%). This shows that netrin-1 has strong cardioprotective effects. Further, netrin-1 perfusion may also inhibit coronary restenosis via its production of nitric oxide to scavenge reactive oxidative species. It has also been shown to activate angiogenic pathways, facilitating the formation of new blood vessels and cardiac repair. Thus, this invention has advantages over current therapies, and may even be used in conjunction with some of those therapies as well.
Patent Number: US20130157944A1
Application Number: US13698541A
Inventor: Cai, Hua
Priority Date: 28 May 2010
Priority Number: US20130157944A1
Application Date: 16 Nov 2012
Publication Date: 20 Jun 2013
IPC Current: A61K003818 | A61K0031519 | C12N0005071 | C12N0005074
US Class: 5140076 | 435375
Assignee Applicant: The Regents of the University of California
Title: Treatment of Myocardial Infarction and Vascular Injury with Netrin-1
Usefulness: Treatment of Myocardial Infarction and Vascular Injury with Netrin-1
Summary: For treating, inhibiting or reducing ischemia/reperfusion injury of a cardiac tissue; for treating, inhibiting, or reducing loss of deleted in colorectal cancer (DCC) protein and mRNA expression in a cardiac tissue; decreasing or reducing the infarct size of a heart resulting from ischemia/reperfusion injury; for decreasing or reducing superoxide production by a cardiac tissue caused by ischemia/reperfusion injury; for treating, inhibiting, or reducing loss of NOS uncoupling in a cardiac tissue; for treating, inhibiting, or reducing mitochondrial damage in a cardiac tissue; for treating, inhibiting, or reducing neointimal formation and restenosis; for treating, inhibiting, or reducing vascular smooth muscle cell proliferation and migration; for increasing vascular smooth muscle cell DCC activation; for treating, inhibiting, or reducing apoptosis of endothelial progenitor cells; for increasing endothelial cell progenitor survival by pre-conditioning; and/or a blood vessel (such as an artery, a coronary artery, a vein, or a capillary) or a portion of the blood vessel (all claimed).
Novelty: Decreasing infarct size of heart resulting from ischemia involves contacting with netrin-1, attenuating superoxide production and nicotinamide adenine dinucleotide phosphate oxidase 4 expression or reducing nitric oxide synthase uncoupling
診斷/治療
癌症/腫瘤
9050298
State Of Development Background Related Materials Netrin-1 prevents ischemia/reperfusion-induced myocardial infarction via a DCC/ERK1/2/eNOS s1177/NO/DCC feed-forward mechanism Additional Technologies by these Inventors Tech ID/UC Case 21477/2010-769-0 Related Cases 2010-769-0
Currently, there are a few treatments available for myocardial infarction. However, these treatments do have undesirable consequences. Drug-eluting stents are often used after angioplasty, which works acutely but often lead to restenosis. Stem cell therapy is theoretically less toxic and adequately repairs damaged heart muscles, but its mechanisms are unclear and does not always work. Other treatments may help reduce heart load or inhibit processes such as thrombosis and pulmonary edema, but are not directly helpful in reducing infarct size.
Netrin-1 induces angiogenesis via a DCC-dependent ERK1/2-eNOS feed-forward mechanism
美國
