Methods of treating myointimal proliferation

Abstract

The present invention provides a method of treating myointimal proliferation by administering a recombinant human soluble ectonucleotide pyrophosphatase phosphodiesterase (hsNPP1), active fragment or fusion protein thereof.

1 .- 23 . (canceled) 
     
     
         24 . A method for determining the effect of ectonucleotide pyrophosphatase pyrophosphorylase 1 (NPP1) treatment on intimal hyperplasia in response to a mechanical injury to a vasculature in an animal model of generalized arterial calcification of infancy (GACI), wherein the animal model is a tip-toe walking (ttw) mouse, the method comprising:
 measuring intimal hyperplasia in the vasculature of the animal following treatment with an NPP1 polypeptide, wherein the animal has been administered the NPP1 polypeptide prior to mechanical injury, following mechanical injury, or both prior to and following a mechanical injury to the vasculature of the animal, wherein the mechanical injury is carotid artery ligation and   comparing the intimal hyperplasia in the animal treated with the NPP1 polypeptide with a control animal that has been treated with vehicle and not with the NPP1 polypeptide,   thereby determining the effect of treatment with the NPP1 polypeptide on intimal hyperplasia in response to the mechanical injury of the vasculature.   
     
     
         25 . The method of  claim 24 , wherein the NPP1 polypeptide has been administered subcutaneously. 
     
     
         26 . The method of  claim 24 , wherein the NPP1 polypeptide is a recombinant human NPP1 polypeptide or a recombinant NPP1 fusion protein comprising an Fc region of an immunoglobulin. 
     
     
         27 . The method of  claim 24 , wherein the intimal hyperplasia results in narrowing of the lumen of a vessel. 
     
     
         28 . The method of  claim 24 , wherein the NPP1 polypeptide has been administered prior to carotid artery ligation. 
     
     
         29 . The method of  claim 24 , wherein the NPP1 polypeptide has been administered prior to and following carotid artery ligation. 
     
     
         30 . A method for determining the effect of NPP1 treatment on intimal hyperplasia in response to a mechanical injury to a vasculature in an animal model of GACI, the method comprising:
 measuring intimal hyperplasia in the vasculature of the animal following treatment with an NPP1 polypeptide, wherein the animal has been administered the NPP1 polypeptide prior to mechanical injury, following mechanical injury, or both prior to and following a mechanical injury to the vasculature of the animal, wherein the NPP1 polypeptide is a recombinant human NPP1 polypeptide or a recombinant NPP1 fusion protein comprising an Fc region of an immunoglobulin, and wherein the mechanical injury is carotid artery ligation and   comparing the intimal hyperplasia in the animal treated with the NPP1 polypeptide with a control animal that has been treated with vehicle and not with the NPP1 polypeptide,   thereby determining the effect of treatment with the NPP1 polypeptide on intimal hyperplasia in response to the mechanical injury of the vasculature.   
     
     
         31 . The method of  claim 30 , wherein the NPP1 polypeptide is administered subcutaneously. 
     
     
         32 . The method of  claim 30 , wherein the intimal hyperplasia results in narrowing of the lumen of a vessel. 
     
     
         33 . The method of  claim 30 , wherein the NPP1 polypeptide has been administered prior to carotid artery ligation. 
     
     
         34 . The method of  claim 30 , wherein the NPP1 polypeptide has been administered prior to and following carotid artery ligation. 
     
     
         35 . The method of  claim 34 , wherein the animal model of GACI is a tip-toe-walking (ttw) mouse.