Anticoagulant - rNAPc2
If a platelet and fibrin thrombus completely blocks a blood vessel within the heart, stopping blood supply to the muscle, it causes acute coronary syndrome, which can be characterised by anything from unstable angina to a myocardial infarction.
If a platelet and fibrin thrombus completely blocks a blood vessel within the heart, stopping blood supply to the muscle, it causes acute coronary syndrome, which can be characterised by anything from unstable angina to a myocardial infarction.
The cascade that leads to the formation of these thrombi starts with tissue factor, a transmembrane protein normally present in the blood in minute quantities that catalyses the activation of factor IX and factor X, and ultimately leads to the formation of thrombin and thence fibrin.
Various antiplatelet agents, including clopidogrel and aspirin, but these do not prevent thrombin generation, and this may explain why the rates of recurrent ischaemic events after clot-busting treatment remain high. Anticoagulants such as heparin or thrombin inhibitors can be used to prevent further clotting but side effects such as bleeding are common. A potential alternative, being developed by Nuvelo under licence from Dendreon, is rNAPc2, a protein isolated from the parasitic hookworm Ancylostoma caninum, which feeds on blood.
Several trials have been carried out. In a multicentre, randomised, double blind, placebo-controlled trial, escalating doses of between 3.5 and 10µg/kg rNAPc2were given to 154 patients undergoing heart bypass surgery, along with aspirin, clopidogrel and unfractionated heparin.1 Major bleeding was more likely in those given the highest doses, and systemic thrombin generation was suppressed in all those given the new drug to below pre-treatment levels for at least 36 hours.
It has also been investigated in a multicentre double blind, placebo controlled Phase IIa trial, in combination with other anticoagulants.2 A total of 200 patients with acute coronary syndrome, were given an intravenous dose of between 1.5 and 10µg/kg, plus a heparin and either aspirin or clopidogrel. By adding rNAPc2 to standard antithrombotic therapy, a dose related inhibition of thrombin was observed, without any increase in clinically significant bleeding. Trials continue.