Methods of inhibiting ectopic calcification

#1. Field of the Invention

#This invention relates generally to the field of medicine and, more specifically, to methods of inhibiting ectopic calcification.

#2. Background Information

#FIGS. 1a) and b) shows the nucleotide (SEQ ID NO:1) and amino acid sequence (SEQ ID NO:2) of human osteopontin, as described by Kiefer et al., Nucleic Acids Res. 17:3306 (1989).

#FIG. 2 shows the effects of osteopontin (a) on calcification of BASMC as compared to vitronectin and fibronectin (b).

#FIG. 3 shows the effects of osteopontin on alkaline phosphatase activity of BASMC (a) and phosphorous concentration in the medium (b) and the effects of levamisole and osteopontin (OPN) on alkaline phosphatase (ALP) activity (c).

#The invention is directed to an effective method for the inhibition of ectopic calcification. Ectopic calcification commonly occurs in association with renal failure, cardiovascular disease, diabetes and the aging process. Ectopic calcification of the vasculature increases an individual's risk of myocardial infarction, ischemia, stroke, dissection after angioplasty and heart valve failure. Ectopic calcification of prosthetic implants, such as bioprosthetic heart valves, is the leading cause of implant failure. Therefore, the method will reduce disease and death associated with ectopic calcification.

#The method is based on the discovery that osteopontin is able to effectively and specifically inhibit ectopic calcification. Therefore, ectopic calcification can be prevented or treated by administering a therapeutically effective amount of osteopontin or a functional fragment thereof to an individual, either systemically or at the predicted or known sites of ectopic calcification. As osteopontin is normally found in calcified tissues and at the sites of ectopic calcification, it can be administered with minimal toxic or immunogenic side effects.

#As used herein, the term “ectopic calcification” is intended to mean the abnormal deposition of calcium crystals at sites other than bones and teeth. Ectopic calcification results in the accumulation of macroscopic hydroxyapatite deposits in the extracellular matrix.