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Lookup NU author(s): Amelia Stennett, Kallie Friston, Professor Claire Harris, Dr Adam WollmanORCiD, Dr Agnieszka Bronowska, Dr Kate HarrisORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Introduction: Complement-based drug discovery is undergoing a renaissance, empowered by new advances in structural biology, complement biology and drug development. Certain components of the complement pathway, particularly C1q and C3, have been extensively studied in the context of neurodegenerative disease, and established as key therapeutic targets. C5 also has huge therapeutic potential in this arena, with its druggability clearly demonstrated by the success of C5-inhibitor eculizumab. Areas covered: We will discuss the evidence supporting C5 as a target in neurodegenerative disease, along with the current progress in developing different classes of C5 inhibitors and the gaps in knowledge that will help progress in the field. Expert opinion: Validation of C5 as a therapeutic target for neurodegenerative disease would represent a major step forward for complement therapeutics research and has the potential to furnish disease-modifying drugs for millions of patients suffering worldwide. Key hurdles that need to be overcome for this to be achieved are understanding how C5a and C5b should be targeted to bring therapeutic benefit and demonstrating the ability to target C5 without creating vulnerability to infection in patients. This requires greater biological elucidation of its precise role in disease pathogenesis, supported by better chemical/biological tools.
Author(s): Stennett A, Friston K, Harris CL, Wollman AJM, Bronowska AK, Madden KS
Publication type: Review
Publication status: Published
Journal: Expert Opinion on Therapeutic Targets
Year: 2023
Volume: 258
Print publication date: 05/10/2023
Online publication date: 14/02/2023
Acceptance date: 03/02/2023
ISSN (print): 1472-8222
ISSN (electronic): 1744-7631
Publisher: Taylor and Francis Ltd.
URL: https://doi.org/10.1080/14728222.2023.2177532
DOI: 10.1080/14728222.2023.2177532
PubMed id: 36786123
