Preclinical concept studies showing advantage of an inhaled anti-CTGF/CCN2 protein for pulmonary fibrosis treatment
Inhaled therapeutics have high potential for the treatment of chronic respiratory diseases of high unmet medical need, such as idiopathic pulmonary fibrosis (IPF). Preclinical and early clinical evidence show that cellular communication network factor 2 (CCN2), previously called connective tissue growth factor (CTGF), is a promising target for the treatment of IPF. In recent phase 3 clinical trials, however, systemic CCN2 inhibition failed to demonstrate a clinically meaningful benefit. Here, we present the preclinical profile of the inhaled anti-CCN2 Anticalin® protein PRS-220. Our study demonstrates that efficient pulmonary delivery directly translates into superior efficacy in relevant models of pulmonary fibrosis when compared to systemic CCN2 inhibition. Moreover, we present a holistic approach for the preclinical characterization of inhaled PRS-220 from state-of-the art in vitro and in vivo models to novel human ex vivo and in silico models, highlighting the advantage of inhaled drug delivery for treatment of respiratory disease.
Authors
- Cornelia Wurzenberger
- Maximilian J. Grill (ORCID: https://orcid.org/0000-0003-1680-0259)
- Marina Pavlidou
- Stefan Grüner (ORCID: https://orcid.org/0000-0002-3757-7677)
- J. Peper-Gabriel
- Oliver Eickelberg (ORCID: https://orcid.org/0000-0001-7170-0360)
- Kei W. Müller (ORCID: https://orcid.org/0009-0004-0744-1623)
- Konrad Höetzenecker (ORCID: https://orcid.org/0000-0001-6775-7460)
- Adriana Estrada‐Bernal (ORCID: https://orcid.org/0000-0002-0555-2766)
- Gabriele Matschiner
- Sandra Kerstan
- Eva-Maria Hansbauer (ORCID: https://orcid.org/0000-0003-4633-2644)
- Shane A. Olwill
- Thomas J. Jaquin (ORCID: https://orcid.org/0000-0002-4389-7554)
- Antonio Konitsiotis
- Jonas Biehler (ORCID: https://orcid.org/0000-0003-3032-1924)
- Joe A. Wrennall
- Vanessa Neiens (ORCID: https://orcid.org/0009-0007-8945-4883)
- Robert Tarran (ORCID: https://orcid.org/0000-0002-8598-2642)
- Poornima Mahavadi (ORCID: https://orcid.org/0000-0002-7580-4738)
- Janette K. Burgess (ORCID: https://orcid.org/0000-0001-9868-9966)
- Mark E. Snyder (ORCID: https://orcid.org/0000-0002-0092-9296)
- Claudia Wurzenberger
- Kentaro Noda (ORCID: https://orcid.org/0000-0001-8921-1944)
- Theresia Mosebach
- Karl-Robert Wichmann (ORCID: https://orcid.org/0009-0002-2879-6613)
- Kristina Heinig
- Athanasios Fysikopoulos (ORCID: https://orcid.org/0000-0002-8081-0198)
- Andreas Güenther (ORCID: https://orcid.org/0000-0002-2187-0975)
- Mary Fitzgerald (ORCID: https://orcid.org/0000-0003-1393-6484)
- Marleen Richter
- Nicolas Schwenck
- Denis Bartoschek
Institutions
- University of North Carolina at Chapel Hill (US)
- University Medical Center Groningen (NL)
- University of Pittsburgh (US)
- Justus-Liebig-Universität Gießen (DE)
- Cobuilder (Norway) (NO)
- Pieris Pharmaceuticals (United States) (US)
- Universities of Giessen and Marburg Lung Center (DE)
- European Clinical Research Infrastructure Network (FR)
- Evangelische Kliniken Gelsenkirchen (DE)
- Cardio-Pulmonary Institute (DE)
- Technische Hochschule Mittelhessen (DE)
- Medical University of Vienna (AT)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-05
- DOI
- https://doi.org/10.1038/s41467-025-58568-x
- Citations
- 10
- Primary Topic
- Connective Tissue Growth Factor Research
- Type
- article
- Field-Weighted Citation Impact
- 8.06