Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - CURE (Constructing a ‘Eubiosis Reinstatement Therapy’ for Asthma)

Teaser

The asthma pandemic imposes a huge burden on patients and health systems in both developed and developing countries. Notwithstanding major efforts in untangling its pathophysiology, we are not even close to reaching a cure. Despite available treatments, symptom control is...

Summary

The asthma pandemic imposes a huge burden on patients and health systems in both developed and developing countries. Notwithstanding major efforts in untangling its pathophysiology, we are not even close to reaching a cure. Despite available treatments, symptom control is generally suboptimal and hospitalisations and deaths remain at unacceptably high levels. This calls for disruptive innovation towards a long-term treatment strategy.
Asthma is an inflammatory condition associated with immune deviations, most often atopic allergy. However, a key characteristic of asthma that remains relatively unexplored is susceptibility to infection. Most acute asthma attacks follow upper respiratory infections; infections are also associated with asthma initiation and persistence.
Recent studies reveal that the respiratory microbiome is characteristically imbalanced in asthma (dysbiosis). Our own data indicate that a feature of dysbiosis in asthma is reduced abundance of bacteriophages (phages). These bacterial viruses infect and are able to naturally control bacterial populations. Phage therapy has been grossly neglected in the western world and is currently just appearing as a novel tool against infection. However, it has never been used for rebalancing dysbiosis in humans.
We propose that reinstating a balanced microbiome (eubiosis) within the asthmatic airway through phage therapy is feasible and will be able to control the immune dysregulation and clinical presentation of the disease. To achieve this, we must be able to predict the effects of adding phage mixtures to the complex ecology of the airways and design appropriate interventions. In CURE, we will develop a predictive model using information from virus-bacteria interactions, host responses and clinical disease expression, validated and fine-tuned using an in-vitro host-microbe-phage interface system. The project will develop phage preparations as candidates for clinical testing in asthma.

Work performed

During the first year of the project, cohorts of patients with asthma and controls have been established to obtain samples for longitudinal dynamics assessment; in addition, the temporal and geographical variation of the respiratory metagenome has been assessed in samples from a previous cohort. This data, together with data that is been produced from the CURE cohorts have been provided in order to start the modeling. Furthermore, initial evaluation and characterization of the immune responses to phages, as well as interactions between phages and the respiratory mucosa have been performed. Significant effort has been put towards isolating phages for bacteria that appear to be relevant in asthma dysbiosis, without however being able to identify new strains.

Final results

The achievement of the CURE Objectives will have major impact upon science and technology, both directly and through enabling new research and innovation potential on a number of domains, including respiratory metagenomics, prediction software and phage technologies. Importantly, CURE will transform phage therapeutic technology and spearhead a new industry: while phage therapy is currently re-emerging in the Western world and tries to find its place in the medical and regulatory environments, CURE will kick-start a new European research and innovation domain around it.

Website & more info

More info: https://www.cureasthma.eu.