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The challenges with familial pulmonary fibrosis
Interstitial Lung Diseases are a group of often fatal lung diseases that cause inflammation and scarring (fibrosis) of the lungs. These diseases include pulmonary fibrosis, cystic fibrosis and certain types of pneumonia.
‘The challenge with FPF is that it’s difficult to diagnose precisely,’ says Professor Gill.
‘Screening for the genetic mutations that cause the disease is complex as there are many rare mutations that could be involved. Screening and diagnosis therefore, need many different experts including those in clinical genetics, bioinformatics and respiratory medicine. Treatment or disease management plans need to be highly personalised to the individual.
‘Our Position Paper has resulted in a roadmap of actions which need to be addressed in order to progress with finding and testing new treatments that specifically target FPF.’
The life expectancy for ILD patients depends on the cause and severity of the specific disease but genetically inherited forms of ILD, in particular FPF, tend to have a poor prognosis and do not respond well to current treatments. The life expectancy of an adult diagnosed with the most severe form of ILD is around three to five years after diagnosis. ILD in children (chILD) includes more than 200 rare and severe genetic lung disorders which can lead to death at birth or within the first years of life.
While clinical trials of repurposed drugs are ongoing and medications and treatments are in development, these do not specifically target FPF. Lung transplant is currently the only effective treatment for children.
Biobanks crucial for new insights and drug discovery
The paper details how more specific gene therapies and tailored gene delivery methods are needed to treat FPF, but there are significant barriers to this advancement, including limited availability of tissue from patients for preclinical research.
The collection of clinical information and associated biomaterials from patients is crucial for investigating the disease, contributing to the successful classification of the disease and becoming an efficient tool to assess diagnostic and therapeutic needs. Researchers say that better collaboration between researchers in Europe and developing countries could contribute to an additional registry of patients with ILD. Combined with existing registries in EU, USA, Australia, this could provide more robust information about rare and common variants of FPF, although there are also challenges around legal and ethical compliance across international boundaries which restrict sharing.
Absence of reliable preclinical models barrier to progress
Preclinical animal models, typically mice, can recapitulate features of human disease and are considered the ‘gold standard’ for proving that a therapy has a chance of working, which can then support clinical trials in humans. The paper details how reliable mouse models are currently limited because the fibrosis induced in the model, does not progress in the same way as a human disease. As a result, these models can’t be used to predict the effectiveness of potential therapies in humans.
Professor Gill explains: ‘Without a good pre-clinical model, we have to rely on cells grown in various culture conditions, outside of any animal body, to demonstrate biological effects of a given therapy, which isn’t ideal.
‘It is important to increase the complexity of available preclinical models so we can examine the cellular interactions which are responsible for initiating and progressing disease.’
Patients can help to find precision treatments
The working group of experts included one FPF patient representative who described the importance of close collaborations between patients and clinical researchers. Providing clear communication to patients about the research from the outset, regular formal updates, and an explanation of the final results of the research directly to patients, fosters trust and can lead to further support for the research effort needed to find new treatments for FPF.
The Position Paper, A roadmap to precision treatments for familial pulmonary fibrosis, is published by The Lancet.