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“All researchers working on asthma should explore completely novel ways to tackle asthma and to prevent it”.

Interviewee: Nikos Papadopoulos, Professor at the National and Kapodistrian University of Athens

Interviewer: Isabel Proaño, Communications Manager at the European Federation of Allergies and Airways Diseases Patients’ Associations (EFA)

CURE, a research project funded by the EU programme Horizon 2020, proposes a phage therapy to control the immune dysregulation of asthma and eventually be able to cure it. To achieve this, the project consortium will investigate how phage addition impacts the ecology of our airways and will design appropriate interventions to be tested in patients. We talked with Prof. Nikos Papadopoulos, CURE Project Coordinator, from the University of Athens.

Is this microbiome therapy a new approach?

Yes and no. The microbiome is not new to science, because there are as many microbiomes as systems in our body. We are full of bacteria. They colonise us at birth, when we leave our mother’s uterus, and they are part of a system -the microbiome- that remains in our body for a long time. When disease appears, the microbiome is disturbed. At CURE, we are looking for an opportunity to rebalance the structure of the microbiome in the lungs, as a way to fight asthma back.

For example, the understanding of the microbiome is very advanced and right now a similar approach to our theory is already used in kids with severe gastrointestinal problems. By treating them with a faecal transplantation, kids evolve from severe diarrhoea to no symptoms, sometimes really fast! The transplantation of different bacteria has managed to rebalance the ecology of their digestive system.

The novelty we want to bring with CURE is linked to the imbalances we have found in the respiratory microbiome in asthma. Thanks to the data collected in PREDICTA, we could analyse viruses and bacteria in asthmatics. We found out that bacterial viruses -phages- are reduced in asthmatics and therefore we are proposing a virus therapy to balance the bacterial population. This is already used in epidemiological diseases through vaccination, but we think that if we manage to understand the connections between bacteria and virus in ecological diseases like asthma, we will set the basis to rebalance the microbiome and propose a cure in respiratory disease.

That could be an amazing discovery in the treatment of asthma. What are your expectations within the CURE project?

One of the main expectations is to understand in detail how the microbial communities interact between themselves and how they impact the disease. We are carefully looking at their interactions because they determine how change happens, but this will take time to decipher.

We don’t know what causes asthma but there is a huge microscopic network behind the façade of inflammation that could answer it. There are viruses, bacteria, not to mention the million particles that we breathe every day. At the moment, we are searching for dynamics that we can interpret; trends to help us to identify invariable elements in the inflammation to define their behaviour. We have in front of us a huge community to define because these associations already generate by themselves a lot of data in the samples.

We will collect all the data and develop a model to help understand balanced situations and key common points like, for example, which organisms are likely to balance or disrupt the system. It’s very ambitious because it implies to document the relationships between organisms, and these are infinite! But without those relationships we cannot define variations, and it is precisely the understanding of change that could determine if there is a clear potential for cure.

How would that cure for asthma look like?

In some eastern countries, virus therapies are used regularly – even given intravenously to infants -  and Georgia is a pioneer in developing and using phage therapies for almost a century. These treatments were common ground in Russia, Poland and other countries of the ex-soviet Union. But we stopped this research in Western Europe with the discovery of antibiotics. As our society is facing widespread antimicrobial resistance, the use of virus therapy in Europe can propose an alternative, but the regulation does not allow it yet. There is no easy way to turn a phage cocktail into a contemporary western medication, produced every 6 months. Phage therapy will require changes in the reproducibility of medicines, as well as in the conceptions of safety and risk in medicinal treatments. For example, in theory the introduction of a virus can lead the person to a severe infection, but this does not mean that virus therapy will lead to an epidemic.

The European Medicines Agency is digging into the use of a stable specific phage cocktail to start with, but an efficient treatment will need to be more flexible and ‘personalised’, which is not allowed under the current rules. There is a clear need to generate new regulations to embrace these therapies that are coming in many fronts. For example, there is already a clinical trial ongoing to treat severe skin infections, mainly wounds, with viral therapy.

Could then phage therapy for asthma be used in other diseases?

Yes. If our approach demonstrates to be working in asthma, it could work then in other diseases with inflammatory components. The challenge with asthma, despite current research and medication, is that we are stuck on symptoms and we are not working on prevention. We are missing something central. Eventually we will find the missing point to radically change the disease.

Most of the patients think and want therapies that prevent the disease. People with asthma are chronic patients, they are under long term medication that is difficult to take and suppress inflammation in a very contra intuitive way. We are putting pressure on patients where it should not be. We should be proposing better solutions for patients and I think all researchers working on asthma should explore completely novel ways to tackle asthma, to prevent it.

What researchers and expertise are you referring to?

All those that are state-of-the-art in their own fields, like the partners in the CURE consortium who are experts in their domain. We are bringing together many approaches from computational analysis to metagenomics, immune methodologies and new phage culture techniques. However, as asthma is a really complex disease with many aspects, including psychological, nutritional, environmental, etc, there should be no limit to the potential approaches or their combinations. Asthma and allergic diseases are a good example where what is called ‘disruptive innovation’ is needed.

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