Therapeutic angiogenic factors and methods for their use

Abstract

The present invention provides a method of stimulating angiogenesis in a human or animal in need thereof, and also provides a composition comprising an angiogenic factor and a pharmaceutically acceptable carrier. In one embodiment, the method comprises administering to a human or other animal a therapeutically effective amount of an angiogenic factor, such as pleiotropin or a midkine protein, contained in a pharmaceutically acceptable carrier. In one embodiment, the carrier includes a controlled release matrix, such as a polymer, that allows the controlled release of angiogenic factors. The polymer is biodegradable and / or bioerodible, preferably biocompatible. Polymers useful for controlled release include, for example, poly(esters), poly(anhydrides) and poly(amino acids). Polymers include, for example, silk elastin poly(amino acid) block copolymers and poly-lactide-co-glycolide. In another embodiment, angiogenic factors may be provided in a carrier comprising liposomes, such as heterocystic liposomes. Carriers such as liposomes may contain targeting ligands capable of targeting the liposomes to predetermined sites in vivo. Angiogenic factors may be administered to the vasculature, such as the cardiovascular system or the peripheral vasculature. In preferred embodiments, the angiogenic factor is a pleiotrophin or a midkine protein. In another embodiment, there is provided a method of stimulating angiogenesis in a human or animal, the method comprising administering to the human or animal a therapeutically effective amount of a gene transfer vector contained in a pharmaceutically acceptable carrier, the gene transfer vector Can encode pleiotropin or midkine protein. Gene transfer vectors can be, for example, naked DNA or viral vectors, and can be used, for example, in combination with liposomes.

Description

technical field [0001] The present invention generally relates to the use of a therapeutic angiogenic factor, such as pleiotrophin, to promote angiogenesis for the treatment of various indications including cardiovascular disease. Background technique [0002] During embryonic and neonatal growth, polypeptide growth factors play an important physiological role in the timely development of tissues, therefore, their expression is tightly regulated. In contrast, expression of polypeptide growth factor genes is deregulated in tumor cell lines as well as in solid tumors, Cross and Dexter, Cell, 64:271 (1991). [0003] Pleiotropin (PTN) is a secreted growth factor belonging to the heparin-binding growth factor family, Lai et al., Biochem. Biophys. Res. Commun., 187:1113-1121 (1992). Originally, pleiotropin was purified from bovine uterus as a weak mitogen and from neonatal rat brain as an axon outgrowth promoter, Milner et al., Biochem. Biophys. Res. Commun., 165: 1096-1103 (1989...

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Problems solved by technology

In contrast, in tumor cell lines as well as in solid tumors, the expression of polypeptide growth factor genes is out of control, Cross and Dexter, Cell, 64:271 (1991)

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