Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1997-12-29
2000-08-08
Campell, Bruce R.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
424 9321, 4353201, A61K 4800
Patent
active
061002429
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD OF THE INVENTION
The present invention relates to gene therapy, more specifically, to virus-mediated and other forms of gene therapy, and to certain adenovirus constructs useful in the delivery of desired genes. More particularly, the invention relates to adenovirus-mediated delivery of genes useful in the promotion of angiogenesis in the heart, and to methods for the treatment of peripheral vascular disease and diseases of the heart such as myocardial ischemia using such vectors.
BACKGROUND OF THE INVENTION
It has been reported by the American Heart Association (1995 Statistical Supplement), that there are about 60 million adults in the United States that have cardiovascular disease, including 11 million adults who have coronary heart disease. Cardiovascular diseases are responsible for almost a million deaths annually in the United States, representing over 40% of all deaths. In 1995, 1.5 million adults in the United States will carry the diagnosis of angina pectoris, experiencing transient periods of myocardial ischemia resulting in chest pain. About 350,000 new cases of angina occur each year in the United States.
Myocardial ischemia occurs when the heart muscle does not receive an adequate blood supply and is thus deprived of necessary levels of oxygen and nutrients. The most common cause of myocardial ischemia is atherosclerosis, which causes blockages in the blood vessels (coronary arteries) that provide blood flow to the heart muscle. Present treatments include pharmacological therapies, coronary artery bypass surgery and percutaneous revascularization using techniques such as balloon angioplasty. Standard pharmacological therapy is predicated on strategies that involve either increasing blood supply to the heart muscle or decreasing the demand of the heart muscle for oxygen and nutrients. Increased blood supply to the myocardium is achieved by agents such as calcium channel blockers or nitroglycerin. These agents are thought to increase the diameter of diseased arteries by causing relaxation of the smooth muscle in the arterial walls. Decreased demand of the heart muscle for oxygen and nutrients is accomplished either by agents that decrease the hemodynamic load on the heart, such as arterial vasodilators, or those that decrease the contractile response of the heart to a given hemodynamic load, such as beta-adrenergic receptor antagonists. Surgical treatment of ischemic heart disease is based on the bypass of diseased arterial segments with strategically placed bypass grafts (usually saphenous vein or internal mammary artery grafts). Percutaneous revascularization is based on the use of catheters to reduce the narrowing in diseased coronary arteries. All of these strategies are used to decrease the number of, or to eradicate, ischemic episodes, but all have various limitations.
Preliminary reports describe new vessel development in the heart through the direct injection of angiogenic proteins or peptides to treat myocardial ischemia. The several members of the fibroblast growth factor (FGF) family (namely acidic fibroblast growth factor, aFGF; basic fibroblast growth factor, bFGF; fibroblast growth factor-5, FGF-5 and others) have been implicated in the regulation of angiogenesis during growth and development. The role of aFGF protein in promoting angiogenesis in adult animals, for example, was the subject of a recent report. It states that aFGF protein, within a collagen-coated matrix, placed in the peritoneal cavity of adult rats, resulted in a well vascularized and normally perfused structure (Thompson, et al., PNAS, 86:7928-7932, 1989). Injection of bFGF protein into adult canine coronary arteries during coronary occlusion reportedly led to decreased myocardial dysfunction, smaller myocardial infarctions, and increased vascularity in the bed at risk (Yanagisawa-Miwa, et al., Science, 257:1401-1403, 1992). Similar results have been reported in animal models of myocardial ischemia using bFGF protein (Harada, et al., J. Clin. Invest., 94:623-630, 1994, Unger, et al., Am. J. Ph
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Dillmann Wolfgang H.
Giordano Frank J.
Hammond H. Kirk
Beckerleg Anne Marie S.
Campell Bruce R.
The Regents of the University of California
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