Compositions for Treating Ectopic Calcification Disorders, and Methods Using Same

Abstract

The present invention includes compositions and methods for treating disease and disorders associated with pathological calcification or pathological ossification.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 62 / 257,883, filed Nov. 20, 2015, which application is hereby incorporated by reference in its entirety.BACKGROUND OF THE INVENTION[0002]Calcification is the accumulation of calcium salts in a body tissue. It normally occurs during formation of bone, but calcium can also be deposited abnormally in soft tissues such as arteries, cartilage and heart valves. Vascular calcification frequently develops in patients with atherosclerosis, stroke, valvular disease and varicosis. Advanced age and metabolic disorders, including diabetes mellitus are contributing factors.[0003]Ossification refers to the process of bone tissue formation or bone remodeling orchestrated by the osteoblasts. Ossification allows bones to form while a fetus is still in the womb, and also converts various types of connective tissue into bone. The two main processes of ossifica...

AI Technical Summary

Benefits of technology

The invention provides a polypeptide that can be used to treat diseases associated with pathological calcification or ossification, such as vascular calcification and NPP1-related diseases. The polypeptide reduces cellular calcification and can be administered as a pharmaceutical agent. The polypeptide has a unique structure and can be easily produced. The technical effect of the invention is to provide a new tool for the treatment of these diseases.

Problems solved by technology

It normally occurs during formation of bone, but calcium can also be deposited abnormally in soft tissues such as arteries, cartilage and heart valves.

GACI is an ultra-rare neonatal disease characterized by infantile onset of widespread arterial calcifications in large and medium sized vessels, resulting in cardiovascular collapse and death in the neonatal period.

Tempering this apparent progress is the severe skeletal toxicity associated with prolonged use of etridonate in patients with GACI, and the ineffectiveness of bisphosphonates to prevent mortality in some patients even when instituted early.

Further, the limited available data makes it difficult to determine if bisphosphonate treatment is truly protective or reflects the natural history of the disease in less effected patients.

Care for patients with ESRD already consumes more than $18 billion per year in the U.S., a substantial burden for the health care system.

Importantly, patients with kidney failure are unable to appropriately regulate serum mineral balance and tend to retain phosphate that is absorbed from the various dietary components.

A high serum level of phosphate is associated with excessive secretion of parathyroid hormone and a tendency to calcification of the soft tissues, including blood vessels.

Deposition of calcium into the small vessels of the skin causes an inflammatory vasculitis called calciphylaxis, which can lead to gangrene of the skin and underlying tissues, resulting in severe, chronic pain.

Calciphylaxis may necessitate amputation of the affected limb and is commonly fatal, with no effective treatment for this condition.

Calcification of small arteries leads to tissue / skin ischemia, infarction and thrombosis, with patient mortality close to 80%.

Currently there are 450,000 patients on dialysis in the U.S. who are at risk of acquiring CUA, and there is no FDA approved treatments for the disease.

They are usually detected during childhood or adolescence and progress slowly and often unpredictably.

Fibrous thickening of the endocardium and atrioventricular valves can also result in restrictive cardiomyopathy.

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