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Onsdag 12. november 2025, kl. 10:00 - 11:00

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1870-816 Faculty Club

Af Helene Eriksen

The golden age of therapeutic complement intervention began in 2007 with the approval of the C5 inhibitor eculizumab for treating paroxysmal nocturnal hemoglobinuria (PNH). Now a dozen complement inhibitors have been approved for a dozen diseases. Anti-C5 therapy has proven highly beneficial across a range of disorders with diverse pathophysiologies. However, particularly in the hematological disease PNH, it became evident that C5 inhibitors - despite their picomolar affinity and an excess of drug over target - cannot completely suppress activation of the terminal lytic pathway. These clinical observations prompted the development of more proximal inhibitors, including C3 inhibitory peptides (e.g., pegcetacoplan) as well as factor B and factor D inhibitors, which also act as stoichiometric inhibitors but display their own unexpected clinical behaviours.
These findings have spurred detailed mechanistic studies that are reshaping our understanding of complement activation and regulation. The unanticipated effects of stoichiometric inhibitors such as eculizumab and pegcetacoplan have revealed that the cascade behaves more dynamically and flexibly than previously appreciated, with exceptions to long-accepted models emerging at multiple levels.
Such insights are not only refining the conceptual foundations of complement biology but are also guiding the rational design of next-generation inhibitors. This presentation highlights how clinical experience and mechanistic discovery together continue to redefine our understanding of the fundamental principles governing the complement cascade.
MBG Focus Talks in Molecular Biology

MBG Focus Talk: Professor Christoph Schmidt

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