EURIPFNET

"European IPF Network: Natural course, Pathomechanisms and Novel Treatment Options in Idiopathic Pulmonary Fibrosis"

 Partecipanti

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'In the eurIPFnet consortium, leading European basic and clinical scientists in the field of interstitial lung diseases associate to jointly decipher the natural course and molecular pathomechanisms of Idiopathic Pulmonary Fibrosis (IPF) and to develop new therapeutic strategies for patients with IPF. This devastating disease affects about 360.000 patients in the EU and causes a substantial socioeconomic burden. IPF patients experience a gradual decrease in quality of life due to progressive dyspnoe and coughing, and usually die within 3-5 years upon diagnosis. There is currently no approved treatment available. Our translational research programme includes implementation of a European IPF registry (eurIPFreg), in which data with regard to natural course, familiar background and susceptibility factors of IPF will be collected, and of a European IPF biobank (eurIPFbank) of blood, bronchoalveolar lavage fluid, cells and tissue specimen of IPF. In these samples, we will perform transcriptome, proteome, phosphoproteome and lipidome analysis, cellular studies and genetic analysis to unravel the molecular pathways underlying IPF and to identify and establish new diagnostic and prognostic markers. Candidate gene verification will be performed in cell culture and animal studies, including siRNA and gene transfection technologies and development of genetically altered mice and will result in the development of new animal models of IPF. Identification of new therapeutic targets in these models will be followed by rapid commercial exploitation and early preclinical and early clinical evaluation. Ultimately, we wish to establish a unique, sustainable and internationally unrivalled European infrastructure for investigation and treatment of IPF. Our mission statement is straight-forward and clear: “Fighting for improved survival in Idiopathic Pulmonary Fibrosis”.'

Introduzione (Teaser)

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder of unknown origin, which is caused by fibrosis or 'scarring' of the connective tissue of the lung, hampering its proper function. A European consortium investigated the gene expression profile and triggering mechanisms of IPF with the ultimate goal of generating new disease treatments.

Descrizione progetto (Article)

IPF affects over 200 000 people in Europe who show a reduced ability to carry oxygen through their bloodstream. This results in dyspnea, initially exertional, later at rest and ultimately leads to death. The underlying cause of IPF is unknown.

The overall objective of the EU-funded Euripfnet project was to decipher the natural course and molecular mechanisms implicated in the pathology of IPF and to develop new therapeutic strategies.

The consortium established a European IPF registry (eurIPFreg) and a European IPF biobank (eurIPFbank) as a data and biomaterial repository for future research in IPF. Based on these, partners were able to conduct extensive transcriptome, proteome and lipidome analyses that revealed a chronic endoplasmic reticulum (ER) stress-response in the alveolar epithelium. This was accompanied by enhanced infection susceptibility, depletion of enzymatic antioxidants and deterioration of alveolar structure.

Particular attention was given to the interactions between growth factors or proteases and cell-surface receptors, as well as to downstream signalling pathways. The aim was to define the key changes in cellular and protein interactions involved in the secondary fibrotic response to the trigger. To this end, the Wnt and Notch signalling pathways were shown to be important for the maintenance and regeneration of the alveolar epithelium.

Furthermore, researchers developed new mouse models of IPF that reproduced the natural course of different trigger mechanisms. One model mimicked the outcome following application of amiodarone and pepstatin, while another genetic model was based on naturally occurring mutations (Hermansky-Pudlak syndrome genes 1 and 2). Collectively, these models served for screening of various therapeutic agents.

Working towards the identification of better disease-specific markers as well as markers of disease activity, scientists established the IPF peripheral blood cell transcriptome. Future use of this information is expected to facilitate correct diagnosis of IPF or early evaluation of drug efficacy.

The eurIPFnet study significantly advanced IPF research and knowledge on the various disease-triggering mechanisms. Translation of the generated information into clinical practice is envisioned to alleviate the clinical picture of IPF sufferers and improve their quality of life.