A new therapy to treat a rare, fatal, congenital disease - generalized arterial calcification of infancy (GACI) - is suggested in a paper in Nature Communications this week.
Babies born with too little extracellular pyrophosphate (PPi), a potent blocker of mineralization, accumulate calcium in the walls of their blood vessels. This causes vessel stiffness and forces the heart to pump blood more forcefully, eventually leading to heart failure. Given that currently-available treatments come with severe side effects, new therapies are needed.
The generation of extracellular PPi is mediated by an enzyme called ENPP1. Mutations in the gene that provides information for making this enzyme cause GACI in humans and mice.
Ronald Albright and colleagues show that treatment of mice born with GACI with a daily injection of ENPP1 enzyme prevents vascular calcification and mortality. The researchers dosed eight diseased mice with subcutaneous injections of the ENPP1 enzyme daily over 42 days. As a control, they used a similar number of diseased mice that had not received therapy. At the end of the study, all animals with GACI that received enzyme replacement therapy survived without any signs of vascular calcification. Conversely, of the mice predisposed to GACI that had not received therapy, all but one succumbed to the disease. Calcifications reappeared in two mice with GACI that received treatment for only two weeks.
Although the long-term effects of ENPP1 therapy remain to be determined, this study identifies a novel agent that might be used for treatment of GACI and perhaps other, more common diseases of tissue calcification.