Ir-CPI is a protein isolated from saliva of the Ixodes ricinus tick and developed by Bioxodes for the prevention of thrombosis.
Mechanism of action
Ir-CPI is the first in a novel class of antithrombotic molecules isolated from the saliva of Ixodes ricinus tick. This ectoparasite produces salivary substances capable of modulating the host immune responses and to maintain blood in a sufficiently fluid state to acquire and digest their blood meal. This molecule was reported to link and to inhibit the activation of two components (i.e. Factor XI [FXI] and Factor XII [FXII]) of the contact phase pathway of the coagulation, a pathway essential for thrombus stabilization and growth.
Ir-CPI is different from existing marketed anticoagulants as it presents antithrombotic properties (dose-dependent inhibition of both venous and arterial thrombi formation) without disturbing the clotting balance and primary hemostasis. Specific inhibition of FXI and FXII positions Ir-CPI for a number of clinical indications where the contact pathway of coagulation is activated.
Using data from complementary sources, including epidemiological studies and investigations in various animal models, the contact pathway has emerged as a mediator of thrombosis.
Blood coagulation is essential for minimizing blood loss from an injured blood vessel but also contributes to vascular thrombosis. Although it has long been thought that the contact pathway is not important for clotting in vivo, recent data obtained with various animal models indicate that contact phase proteins seem to be essential for thrombus formation.
For decades, anticoagulant treatment has been dominated by compounds that requires careful laboratory testing to guarantee sufficient antithrombotic effectiveness while avoiding the risk of hemorrhage. This disadvantage, together with the relatively narrow therapeutic margin of these drugs, has considerably stimulated research into other types of agents.
Research initiated by E. Godfroid’s former team at the Free University of Brussels showed that intravenous administration of Ir-CPI in rats and mice caused a dose-dependent reduction in venous thrombus formation and revealed a defect in the formation of arterial occlusive thrombi. Remarkably, the effective antithrombotic dose of Ir-CPI did not promote bleeding or impair blood coagulation parameters.