Methods for Treating Conditions Associated with MASP-2 Dependent Complement Activation
In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a living subject suffering from, or at risk for developing a thrombotic microangiopathy (TMA). The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation. In some embodiments, the MASP-2 inhibitory agent inhibits cellular injury associated with MASP-2-mediated alternative complement pathway activation, while leaving the classical (C1q-dependent) pathway component of the immune system intact.
1 . A method of inhibiting MASP-2-dependent complement activation in a subject suffering from Degos disease, comprising administering to the subject a composition comprising an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation.
2 . The method of claim 1 , wherein the MASP-2 inhibitory agent is an anti-MASP-2 antibody or fragment thereof.
3 . The method of claim 2 , wherein the MASP-2 inhibitory agent is an anti-MASP-2 monoclonal antibody, or fragment thereof that specifically binds to a portion of SEQ ID NO:6.
4 . The method of claim 1 , wherein the subject has previously undergone, or is currently undergoing, treatment with a terminal complement inhibitor that inhibits cleavage of complement protein C5.
5 . The method of claim 1 , wherein the method further comprises administering to the subject a terminal complement inhibitor that inhibits cleavage of complement protein C5.
6 . The method of claim 5 , wherein the terminal complement inhibitor is a humanized anti-C5 antibody or antigen-binding fragment thereof.
7 . The method of claim 5 , wherein the terminal complement inhibitor is eculizumab.
8 . The method of claim 2 , wherein the antibody or fragment thereof is selected from the group consisting of a recombinant antibody, an antibody having reduced effector function, a chimeric antibody, a humanized antibody and a human antibody.
9 . The method of claim 1 , wherein the composition is administered subcutaneously, intra-muscularly, intra-arterially, intravenously, or as an inhalant.