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Use of Adenosine Agonists to Prevent Arterial Vascular Calcification Disorder

Scientists at the National Human Genome Research Institute (NHGRI) and the National Heart Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH) have discovered a genetic defect in the Ecto-5’-nucleotidase (NT5E) gene which results in Cluster of Differentiation 73 (CD73) deficiency that leads to a decrease in adenosine, and ultimately, an increase in vascular calcification.NT5Eencodes CD73, an enzyme that converts adenosine monophosphate (AMP) to adenosine in the extracellular region of the vascular endothelium. Normally, extracellular adenosine binds to one of the several receptors on the surface decreasing the production of cyclic AMP (cAMP) resulting in an inhibition of vascular calcification. The discovery of this genetic mutation leading to a decrease in adenosine provides a method of treating or preventing the disorder by using adenosine receptor agonists as therapeutic agents. Adenosine receptor agonists can be used to treat or prevent disorders associated with vascular and/or joint capsule calcification, including for example atherosclerosis, Monkeberg’s medial sclerosis, CD74 deficiency, Ehlers Danlos syndrome (EDS), Marfan/Loewe Dietz syndrome, fibromuscular dysplasia, Kawasaki syndrome, pseudoxanthoma elasticum, and premature placental calcification.
Patent Abstract: 
Scientists at the National Human Genome Research Institute (NHGRI) and the National Heart Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH) have discovered a genetic defect in the Ecto-5’-nucleotidase (NT5E) gene which results in Cluster of Differentiation 73 (CD73) deficiency that leads to a decrease in adenosine, and ultimately, an increase in vascular calcification.NT5Eencodes CD73, an enzyme that converts adenosine monophosphate (AMP) to adenosine in the extracellular region of the vascular endothelium. Normally, extracellular adenosine binds to one of the several receptors on the surface decreasing the production of cyclic AMP (cAMP) resulting in an inhibition of vascular calcification. The discovery of this genetic mutation leading to a decrease in adenosine provides a method of treating or preventing the disorder by using adenosine receptor agonists as therapeutic agents. Adenosine receptor agonists can be used to treat or prevent disorders associated with vascular and/or joint capsule calcification, including for example atherosclerosis, Monkeberg’s medial sclerosis, CD74 deficiency, Ehlers Danlos syndrome (EDS), Marfan/Loewe Dietz syndrome, fibromuscular dysplasia, Kawasaki syndrome, pseudoxanthoma elasticum, and premature placental calcification.
applications 
Inventors: 
William Gahl
Patent Number: 
61/319,336 PCT Application No. PCT/US2011/030493 U
Internal Laboratory Ref #: 
E-094-2010/0
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