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Paroxysmal Nocturnal Hemoglobinuria pp 319–346Cite as

Future Strategies of Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria

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Abstract

The treatment of paroxysmal nocturnal hemoglobinuria (PNH) has dramatically changed since the availability of the first clinical complement inhibitor eculizumab. Eculizumab treatment has been proven terrifically effective in controlling intravascular hemolysis of PNH; however, unmet clinical needs are emerging, starting with the possible occurrence of C3-mediated extravascular hemolysis. Indeed, scientific and commercial reasons have triggered the development of a number of novel anticomplement agents. Different strategies are currently under investigation, which may target distinct steps and pathways of the complement system. Indeed, starting from the anti-C5 therapy that is already in the clinic, novel approaches are investigating the possibility of intercepting the complement cascade upstream, at the level of C3 and C3 convertase or of other initiating factors. Here we will review the majority of these strategies, focusing on available data in PNH and/or other preclinical models. The possible relevance for clinical application in PNH will be highlighted, based on well-established and emerging knowledge of molecular complement derangement in PNH.

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Authors and Affiliations

  1. Hematology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Via Pansini 5, 80131, Naples, Italy

    Antonio M. Risitano M.D., Ph.D.

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  1. Antonio M. Risitano M.D., Ph.D.
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Correspondence to Antonio M. Risitano M.D., Ph.D. .

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  1. Department of Hematology and Ocology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    Yuzuru Kanakura

  2. Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan

    Taroh Kinoshita

  3. Dept of Hematology and Ocology, Osaka University Dept of Hematology and Ocology, Suita, Osaka, Japan

    Jun-ichi Nishimura

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Risitano, A.M. (2017). Future Strategies of Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria. In: Kanakura, Y., Kinoshita, T., Nishimura, Ji. (eds) Paroxysmal Nocturnal Hemoglobinuria. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56003-6_20

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  • DOI: https://doi.org/10.1007/978-4-431-56003-6_20

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