Toggle Main Menu Toggle Search

Open Access padlockePrints

Developments in anti-complement therapy; from disease to clinical trial

Lookup NU author(s): Professor Claire Harris, Professor David Kavanagh, Dr Ruyue Sun

Downloads


Licence

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 2018 The Authors The complement system is well known for its role in innate immunity and in maintenance of tissue homeostasis, providing a first line of defence against infection and playing a key role in flagging apoptotic cells and debris for disposal. Unfortunately complement also contributes to pathogenesis of a number of diseases; in some cases driving pathology, and in others amplifying or exacerbating the inflammatory and damaging impact of non-complement disease triggers. The role of complement in pathogenesis of an expanding number of diseases has driven industry and academia alike to develop an impressive arsenal of anti-complement drugs which target different proteins and functions of the complement cascade. Evidence from genetic and biochemical analyses, combined with improved identification of complement biomarkers and supportive data from sophisticated animal models of disease, has driven a drug development landscape in which the indications selected for clinical trial cluster in three ‘target’ tissues: the kidney, eye and vasculature. While the disease triggers may differ, complement activation and amplification is a common feature in many diseases which affect these three tissues. An abundance of drugs are in clinical development, some show favourable progression whereas others experience significant challenges. However, these hurdles in themselves drive an ever-evolving portfolio of ‘next-generation’ drugs with improved pharmacokinetic and pharmacodynamics properties. In this review we discuss the indications which are in the drug development ‘spotlight’ and review the relevant indication validation criteria. We present current progress in clinical trials, highlighting successes and difficulties, and look forward to approval of a wide selection of drugs for use in man which give clinicians choice in mechanistic target, modality and route of delivery.


Publication metadata

Author(s): Harris CL, Pouw RB, Kavanagh D, Sun R, Ricklin D

Publication type: Article

Publication status: Published

Journal: Molecular Immunology

Year: 2018

Volume: 102

Pages: 89-119

Print publication date: 01/10/2018

Online publication date: 16/08/2018

Acceptance date: 06/06/2018

Date deposited: 29/08/2018

ISSN (print): 0161-5890

ISSN (electronic): 1872-9142

Publisher: Pergamon Press

URL: https://doi.org/10.1016/j.molimm.2018.06.008

DOI: 10.1016/j.molimm.2018.06.008


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share