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Preclinical and translational research to discover potentially effective antifibrotic therapies in systemic sclerosis


Jordan, Suzana; Chung, James; Distler, Oliver (2013). Preclinical and translational research to discover potentially effective antifibrotic therapies in systemic sclerosis. Current Opinion in Rheumatology, 25(6):679-685.

Abstract

PURPOSE OF REVIEW: To discuss the strategies for preclinical and early clinical characterization of targeted antifibrotic therapies in order to optimize the probability of positive results in later stage clinical trials.

RECENT FINDINGS: There is a high unmet clinical need for effective antifibrotic therapies in systemic sclerosis (SSc), and in parallel a rapid development in the identification of potential molecular targets in preclinical research. Herein, we discuss the strategies for the improvement of preclinical and early clinical trials. These strategies include identification and characterization of molecular targets for therapy in vitro, selection of relevant parameters in translational animal models, confirmation of target activation in human SSc, analysis of successful target coverage after drug exposure in human SSc, and conduct of biomarker-driven proof-of-concept studies as a bridge between animal studies and Phase IIB/III studies with clinical endpoints.

SUMMARY: These strategies could increase the possibility to develop successful drugs against the fibrotic manifestations of SSc.

Abstract

PURPOSE OF REVIEW: To discuss the strategies for preclinical and early clinical characterization of targeted antifibrotic therapies in order to optimize the probability of positive results in later stage clinical trials.

RECENT FINDINGS: There is a high unmet clinical need for effective antifibrotic therapies in systemic sclerosis (SSc), and in parallel a rapid development in the identification of potential molecular targets in preclinical research. Herein, we discuss the strategies for the improvement of preclinical and early clinical trials. These strategies include identification and characterization of molecular targets for therapy in vitro, selection of relevant parameters in translational animal models, confirmation of target activation in human SSc, analysis of successful target coverage after drug exposure in human SSc, and conduct of biomarker-driven proof-of-concept studies as a bridge between animal studies and Phase IIB/III studies with clinical endpoints.

SUMMARY: These strategies could increase the possibility to develop successful drugs against the fibrotic manifestations of SSc.

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4 citations in Web of Science®
5 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Date:2013
Deposited On:06 Jan 2014 12:33
Last Modified:05 Apr 2016 17:19
Publisher:Lippincott, Williams & Wilkins
ISSN:1040-8711
Publisher DOI:https://doi.org/10.1097/01.bor.0000434598.51526.0e
PubMed ID:24047603

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