Optimizing human apyrase to treat arterial thrombosis and limit reperfusion injury without increasing bleeding risk

How useful would this be in limiting the reperfusion  damage post tPA usage? What will your doctor and hospital do to change stroke protocols based on this?  ANYTHING AT ALL? Do they ever do anything to help stroke survivors?
http://stm.sciencemag.org/content/6/248/248ra105.abstract

1. Douglas Moeckel¹,
2. Soon Soeg Jeong²,
3. Xiaofeng Sun³,
4. M. Johan Broekman⁴,⁵,
5. Annie Nguyen¹,
6. Joan H. F. Drosopoulos⁴,⁵,
7. Aaron J. Marcus⁴,⁵,
8. Simon C. Robson³,
9. Ridong Chen²,* and
10. Dana Abendschein¹,*

+ Author Affiliations

1. ¹Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
2. ²APT Therapeutics Inc., 4041 Forest Park Avenue, St. Louis, MO 63108, USA.
3. ³Division of Gastroenterology/Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
4. ⁴Thrombosis Research Laboratory, Research Service, Veterans Affairs New York Harbor Healthcare System, New York, NY 10010, USA.
5. ⁵Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA.

1. ↵*Corresponding author. E-mail: rchen@apt-therapeutics.com (R.C.); dabendsc@DOM.wustl.edu (D.A.)

Abstract

In patients with acute myocardial infarction undergoing reperfusion therapy to restore blood flow through blocked arteries, simultaneous inhibition of platelet P2Y₁₂ receptors with the current standard of care neither completely prevents recurrent thrombosis nor provides satisfactory protection against reperfusion injury. Additionally, these antiplatelet drugs increase the risk of bleeding. To devise a different strategy, we engineered and optimized the apyrase activity of human nucleoside triphosphate diphosphohydrolase-3 (CD39L3) to enhance scavenging of extracellular adenosine diphosphate, a predominant ligand of P2Y₁₂ receptors. The resulting recombinant protein, APT102, exhibited greater than four times higher adenosine diphosphatase activity and a 50 times longer plasma half-life than did native apyrase. Treatment with APT102 before coronary fibrinolysis with intravenous recombinant human tissue-type plasminogen activator in conscious dogs completely prevented thrombotic reocclusion and significantly decreased infarction size by 81% without increasing bleeding time. In contrast, clopidogrel did not prevent coronary reocclusion and increased bleeding time. In a murine model of myocardial reperfusion injury caused by transient coronary artery occlusion, APT102 also decreased infarct size by 51%, whereas clopidogrel was not effective. These preclinical data suggest that APT102 should be tested for its ability to safely and effectively maximize the benefits of myocardial reperfusion therapy in patients with arterial thrombosis.