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Drugs Fut 2020, 45(6): 389
ISSN 0377-8282
e-ISSN 2013-0368
Copyright 2020 Clarivate
CCC: 0377-8282
DOI: 10.1358/dof.2020.45.6.3115216
MASP-2 inhibition as a potential strategy for the management of IgA nephropathy
Barratt, J., Lafayette, R.
Although the complement system supports innate host defense against pathogens, inappropriate or over-activation can lead to serious disease, such as in immunoglobulin A nephropathy (IgAN). Currently, the only marketed drugs that specifically target the complement system are a C1 esterase inhibitor and monoclonal antibodies that bind to complement protein C5. The lectin pathway plays a dominant role in activating complement in IgAN, and selective lectin pathway inhibition with mannose-binding lectin-associated serine protease-2 (MASP-2) inhibitors would provide a treatment option that differs from those currently available and offers significant advantages over existing treatments in terms of safety. This article reviews the rationale for targeting the lectin pathway as well as the potential effects of lectin pathway inhibition in terms of infections, and briefly discusses narsoplimab (OMS- 721), a human IgG4 monoclonal antibody that binds to and inhibits MASP-2 that is currently in development for the treatment of IgAN, thrombotic microangiopathies, glomerulopathies and other diseases mediated by the lectin pathway of complement.

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