Interstitial lung disease (ILD) in adults and children (chILD) is a group of devastating fatal lung diseases leading to scarring of the lung and death often within 3 years of diagnosis. While new antifibrotic drugs offer hope of slowing disease progression in adults, no effective treatments are available for children and lung transplant is the only effective cure. Genetic factors may cause or contribute significantly to the risk of developing ILDs and those patients with inherited forms of ILD may have a worse prognosis than sporadic-ILD, respond poorly to current treatments and some can have serious adverse reactions to immunosuppression after transplantation. Across Europe diverse mutations including those in genes related to telomere homeostasis, and more rarely in surfactant homeostasis can lead to abnormal cell aging and surfactant protein processing in lung alveolar epithelial cells respectively. The rarity of individual mutations contributes to a lack of basic mechanistic studies and randomised control trial data on effectiveness of treatments. Consequently, management strategies derive from other diseases are based on physicians experience and remain controversial. Furthermore, the current-state-of-the-art preclinical models fail to accurately recapitulate the diverse genetic causes of ILD. Therefore, there is a lack of effective preclinical tools that can be shared with researchers across Europe to study these diseases in order to identify and personalise treatments for patients. Members of the CIG have already employed patient-derived geneedited induced pluripotent stem cells to generate alveolar epithelial cells and macrophage and successfully model ILD and other chronic lung diseases in vitro. The CIG has already established nascent collaborative relationships to use these cells to study this group of diseases and to test novel treatments. The European Network for Translational Research in Children’s and Adult ILD (ENTeR chILD) a network of multidisciplinary clinicians (paediatric and adult), scientists, and patients and their families has already initiated pan-European research with the ultimate goals to deliver accurate and early diagnosis with structured, personalised, management and therapies. In partnership with patient organisations, we have co-designed a groundbreaking proposal which aims to leverage this existing transdisciplinary network to establish a first-of-a-kind Europe-Wide open-access resource of patient-derived iPSC linked with highly phenotyped patient data. We believe the establishment of this resource will foster a growing body of research across Europe to develop a robust preclinical model of ILD that can a) explore pathogenesis b) identify new patient-specific druggable targets and c) test novel compounds and inhaled modes of delivery for patients in vitro before clinical studies, leading to shortening of drug development pipelines and reduction of toxic side effects.
Induced pluripotent stem cells - Interstitial lung disease - Biobank - Childrens interstitial lung disease - Disease modelling of alveolar cells and macrophage
|Action Vice Chair|
|Grant Holder Scientific Representative|