Researchers at Helmholtz Zentrum München, in collaboration with an international team, have identified a potential novel drug target for idiopathic pulmonary fibrosis, a dangerous chronic lung disease. They elucidated a new mechanism of fibrosis formation that plays an important role in the pathogenesis of the disease. These findings have now been published in the leading scientific journal American Journal of Respiratory and Critical Care Medicine.
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease for which as yet no causal therapy exists. It is, however, known that the lung interstitium – the connective tissue between the air sacs in the lower part of the lung – is affected.
Foto: Staab-Weijnitz, Eickelberg
There scar tissue consisting mainly of collagen accumulates, thus reducing lung elasticity and gradually impairing lung function. Patients with IPF have an extremely poor prognosis; on average they survive only two or three years after the diagnosis has been made.
Analysis of patient data
Prof. Dr. Oliver Eickelberg and Dr. Claudia Staab-Weijnitz of the Comprehensive Pneumology Center (CPC) at Helmholtz Zentrum München and their colleagues at LMU University Hospital in Munich and Yale University School of Medicine have now discovered a new therapeutic target for IPF.
The main focus of their research was to identify causative mechanisms involved in the disease. The researchers analyzed microarray data of samples from German patients and from an IPF cohort of the Lung Tissue Research Consortium in the U.S.
The analysis revealed elevated levels of the protein FKBP10 in the lungs of IPF patients. The researchers hypothesized that if the production or activity of the protein could be inhibited, this might lead to a new therapeutic approach. Further experiments confirmed that knockdown of this protein in IPF fibroblasts* diminished the collagen synthesis.
“Thus, FKBP10 represents a potential new target molecule for the individualized therapy of IPF,” said Claudia Staab-Weijnitz. “In the future, these results could also lead to new therapeutic options for the treatment of other fibrotic** diseases.”
New ways to understand the disease cause
Eickelberg has made the study of IPF one of his key priority research areas. Together with his team of researchers, he is studying the pathogenic mechanisms with the aim to develop causal therapies – and thus one day to actually cure IPF. In the short term, however, the main focus is on delaying the progression of the disease and alleviating the symptoms.
“My foremost objective is to help develop an effective treatment that will completely halt the progression of IPF in the patient,” said Eickelberg. “These approaches are best developed in international networks. This cooperative project is a direct result of the research stay of Professor Kaminski (Yale) at the CPC through the support of a Helmholtz International Fellow Award (HIFA).”
“With our translational approach,” said Eickelberg, “we want to help alleviate the suffering of patients with lung disease.” In the case of IPF, the researchers now want to establish a drug screening assay and begin clinical trials with an FKBP10 inhibitor, an agent to inhibit the production or activity of the FKBP10 protein.
*Fibroblasts: Fibroblasts are motile cells that are present in connective tissue. They play an important role in the synthesis of the extracellular matrix, the connective tissue between the cells. The products of fibroblasts primarily include collagen as well as proteoglycans, which strengthen the extracellular matrix.
**Fibrotic diseases are accompanied by an excessive proliferation of connective tissue.
Staab-Weijnitz C. A. et al. (2015). FK506-Binding Protein 10 is a Potential Novel Drug Target for Idiopathic Pulmonary Fibrosis, American Journal of Respiratory and Critical Care Medicine [Epub ahead of print]
As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. www.helmholtz-muenchen.de
The Comprehensive Pneumology Center (CPC) is a joint research project of the Helmholtz Zentrum München, the Ludwig-Maximilians-Universität Clinic Complex and the Asklepios Fachkliniken München-Gauting. The CPC's objective is to conduct research on chronic lung diseases in order to develop new diagnosis and therapy strategies. The CPC maintains a focus on experimental pneumology with the investigation of cellular, molecular and immunological mechanisms involved in lung diseases. The CPC is a site of the Deutsches Zentrum für Lungenforschung (DZL).
Contact for the media
Department of Communication, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, 85764 Neuherberg - Phone: +49-(0)89-3187-2238 - Fax: +49 89-3187-3324 - Email: email@example.com
Scientific contact at Helmholtz Zentrum München:
Professor Oliver Eickelberg, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Institut für Lungenbiologie, Comprehensive Pneumology Center - Phone: +49-89-3187-4666 – Email: firstname.lastname@example.org
Location Neuherberg: Ingolstädter Landstr. 1, 85764 Neuherberg,
Location Großhadern: Max-Lebsche-Platz 31, 81377 München
http://www.ncbi.nlm.nih.gov/pubmed/26039104 - Link to the Original Publication
https://www.helmholtz-muenchen.de/en/index.html - Website Helmholtz Zentrum München
http://www.helmholtz-muenchen.de/ilbd/index.html - Website Institute of Lung Biology and Disease
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