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Updated: May 7, 2026
Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
Preclinical and translational research to discover potentially effective antifibrotic therapies in systemic sclerosis
Suzana Jordan1, James Chung, Oliver Distler
1aDepartment of Rheumatology, University Hospital Zurich, Zurich, Switzerland bAmgen Inc., Thousand Oaks, California, USA.
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.
Insights
Developing effective antifibrotic therapies for systemic sclerosis (SSc) requires improved preclinical and early clinical trial strategies. These approaches aim to increase the success rate of targeted antifibrotic drug development for SSc patients.
Area of Science:
- Fibrosis research
- Translational medicine
- Drug development
Background:
- Systemic sclerosis (SSc) presents a significant unmet need for antifibrotic treatments.
- Preclinical research is rapidly identifying potential molecular targets for SSc therapy.
Purpose of the Study:
- To outline strategies for enhancing preclinical and early clinical characterization of targeted antifibrotic therapies.
- To optimize the likelihood of successful outcomes in later-stage clinical trials for SSc.
Main Methods:
- In vitro identification and characterization of molecular targets.
- Selection of relevant parameters in translational animal models.
- Confirmation of target activation and drug coverage in human SSc.
- Biomarker-driven proof-of-concept studies.
Main Results:
- Proposed strategies address key stages from target identification to early clinical validation.
- Integration of in vitro, animal model, and human SSc data is crucial.
- Biomarker studies serve as a bridge to later-phase clinical trials.
Conclusions:
- Implementing these integrated strategies can improve the development of successful antifibrotic drugs for SSc.
- Enhanced characterization increases the probability of positive results in clinical trials for fibrotic diseases.
