Nuvelo's experimental drug, recombinant nematode anticoagulant protein (rNAPc2), will be used for first-line treatment of metastatic in combination with bevacizumab. This is a "recombinant protein fashioned after one orginally isolated from the saliva of the dog hookworm, " says their Web site.
Studies have been performed on this protein for use as an anticoagulant or anti-angiogenesis agent:
Modulators of the coagulation cascade: focus and recent advances in inhibitors of tissue factor, factor VIIa and their complex. (Curr Med Chem. 2005;12(4):397-417.)
From the abstract:
Recent developments in the field of haemostasis and thrombosis highlighted the crucial role of the tissue factor/factor VIIa complex (TF/FVIIa) in the initiation of coagulation processes. Nowadays, anticoagulant therapies involving heparin or coumarin derivatives, thrombin or factor Xa inhibitors are generally associated with side effects such as bleeding and thrombocytopenia. In this context, the inhibition of TF, FVIIa and their complex by efficient antithrombotic drugs represents a new strategy to reduce this bleeding and to prevent thrombosis events. Moreover, TF/FVIIa inhibition is shown to be useful in the treatment of biological processes independent of the clotting cascade such as angiogenesis and cancer. Among the natural and genetically engineered TF/FVIIa inhibitors, injections of the recombinant protein rNAPc2 show clinical improvements, such as reduced bleeding and thromboembolism, over classical drugs used in the therapy of coronary angioplasty and hip or knee replacement surgery.
Tissue Factor/Factor VIIa Inhibitors Block Angiogenesis and Tumor Growth Through a Nonhemostatic Mechanism (Cancer Res. 2003 Jun 1;63(11):2997-3000.).
This study tested its effect on murine tumors. From the abstract:
An association between cancer and thrombosis has been recognized for more than a century. However, the manner by which tumor growth is regulated by coagulation in vivo remains unclear. To assess the role of coagulation on tumor growth, in vivo, we tested coagulation inhibitors specific for either tissue factor (TF)/factor VIIa (fVIIa) complexes or factor Xa (fXa) for antitumor activity. Here, we show that two inhibitors of TF/fVIIa, TF pathway inhibitor (TFPI) and the nematode anticoagulant protein rNAPc2, inhibit both primary and metastatic tumor growth in mice. In addition, we show that rNAPc2 is also a potent inhibitor of angiogenesis.
