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

Harris, Claire L. and Pouw, Richard B. and Kavanagh, David and Sun, Ruyue and Ricklin, Daniel. (2018) Developments in anti-complement therapy; from disease to clinical trial. Molecular immunology, 102. pp. 89-119.

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Abstract

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.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molekulare Pharmazie (Ricklin)
UniBasel Contributors:Ricklin, Daniel and Pouw, Richard Benjamin
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0161-5890
e-ISSN:1872-9142
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:26 Apr 2019 07:21
Deposited On:26 Apr 2019 07:21

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