Patients, progress and participation in cystic fibrosis research

Patients, progress and participation in cystic fibrosis research
© iStock/ LucaLorenzelli

Hilde De Keyser talks to Health Europa about the importance of involving patients in cystic fibrosis research.

Cystic fibrosis (CF) is an inherited and to date incurable condition that affects the lungs, digestive system and most organs in the body. Continuous improvements in diagnosis and intense, life-long treatment have shifted CF from a childhood disease with a life expectancy of just a few months after birth to a disease of adults. According to the European Cystic Fibrosis Society Patient Registry, 52% of CF patients are now over the age of 18 and patients older than 40 are no longer the exception.1

Working to improve the lives of all CF patients is CF Europe, a federation of national CF associations across 39 European countries. Founded in 2003, the organisation is committed to:

  • Promoting and supporting patient-centred research through collaboration with key stakeholders in CF research
  • Fostering access to high-quality care that puts the patient’s needs first throughout Europe
  • Representing and defending the interests of people with CF to policymakers, industry, healthcare providers etc. at the European level
  • Keeping the CF patient community abreast of research, lobbying and care outcomes and supporting sharing of best practice.

Health Europa recently spoke to Hilde de Keyser, CF Europe’s head of engagement, to find out more about the current research landscape for CF, what opportunities there are for patients to get involved in CF research, and the organisation’s own activities in this space.

Can you highlight some of the most recent areas of progress in cystic fibrosis research?

The development of so-called ‘CFTR modulators’ is without doubt the most exciting and promising breakthrough in CF research in recent years, because these are the first medicines to really tackle the underlying cause of the disease rather than focusing on its symptoms.

Based upon increasing knowledge of the CFTR protein and how it functions, researchers were able to unravel what would be necessary to increase stability of this protein and regain functionality – characteristics which are lost in CF. This led to the development of CFTR modulators, small molecules that are able to increase functionality of the CFTR protein.

Some of these modulators are already available to a subset of CF patients (CF being a group of patients with different mutations and therefore requiring different medicines) in some – but unfortunately not all – countries.

There are several classes of CFTR modulators:

  • Correctors: Small molecules that bind to the misfolded CFTR protein channel and help it reach the cell surface where it can be active
  • Potentiators: Small molecules that improve the function of the channel at the cell surface by helping it to be ‘open’
  • Amplifiers: Small molecules that increase the amount of CFTR protein in the cell so that there is more substrate for the correctors
  • Read-through inducing drugs: A subset of CF patients have so-called ‘stop-codon mutations’, meaning that there is a mutation in their DNA which prevents the DNA from being ‘read’ completely, resulting in a truncated protein that will break down. Read-through inducing drugs enable ‘skipping’ the premature stop-codon so a full-length protein is generated.

This advance is naturally commanding a lot of attention, but at CF Europe, we believe it is vitally important to continue to also focus on airway clearance, pulmonary infections and pulmonary inflammation for patients who are either not eligible for modulator treatment or do not have access to it, as well as for patients with established pulmonary damage.

This research may not be as innovative or as interesting as that of CFTR modulators, but it is nonetheless absolutely crucial, and we are heartened to see a number of companies focusing on this area.

For instance, several companies are working on sodium channel inhibitors. When these channels are inhibited, more sodium will stay in the airways, meaning that water will also stay there. Airways will thus stay hydrated and mucus will more easily be removed from the airways.

Several companies are currently focusing on inhaled nitric oxide (NO). This is a signalling molecule produced by immune cells and occurs naturally in our body. Earlier studies have shown that in high concentrations, NO can kill bacteria, including Mycobacterium abscessus. This raises hope that NO might also be effective against antibiotic-resistant bacteria.

Elsewhere, several pharmaceutical companies are working to develop a myriad of small molecules. What they have in common is that they inhibit the release of pro-inflammatory signalling molecules by the immune cells. This should decrease inflammation and reduce damage to the lungs.

Of course, it is important not to totally inhibit the working of immune cells in the lungs, because they are important to fight bacteria. This is a difficult equilibrium.

In addition to this work, the past months have also seen exciting news emerge from basic science. Just last year, scientists were able to grow or ‘bioengineer’ new lungs from lung cells and transplant them back into the pigs from which the original lung cells were taken.

After monitoring the pigs for two months, none of the transplanted lungs were rejected and all of them were healthy. This research is in its very early stages and it will be a long time before it reaches human studies or patients – the experiment will first have to be repeated on a larger scale and the pigs monitored for a longer period of time in order to evaluate the long-term effects of the transplant. Nonetheless, it is a very exciting development which, if successful, could solve the problem of donor shortages.

On top of that, a new lung cell type called pulmonary ionocyte has been discovered, which researchers believe could play a big role in CF because it expresses far more CFTR channels than other cells found in the airways. The exact role of these cells is still to be revealed, but they might have potential as a target for future therapeutics.

It is a very exciting time to be involved in CF research, and CF Europe, as a patient group, is committed to following these developments as they happen and supporting them in whatever way we can.

What is the importance of engaging patients in cystic fibrosis research?

It is crucial to engage patients in the research process right from its early stages. CF Europe works to align the CF community’s research priorities with the issues that really matter to patients and families – after all, they are the ones who actually live with the disease, so they are best placed to identify gaps in current knowledge and to tell us what is needed to make a real difference in their everyday lives.

In 2018, the Cystic Fibrosis Foundation surveyed clinical researchers, adults with CF and family members about a broad range of research topics that perhaps attract less attention and arrived at three key research priorities:2

  1. Respiratory micro-organism detection and treatment
  2. Mental health
  3. Reducing treatment burden.

These are three very different areas of research, but we know thanks to the survey that they will make a large difference to patients’ quality of life.

CF Europe also believes that there is a real benefit to involving patients and their families as early as possible in the design of clinical trials. Patients can provide valuable real-life input to researchers about the burden and practicality of a so-called ‘trial protocol’, which describes in detail how the medicine will be tested, how patients will be involved and how the data will be analysed.

For instance, we have received feedback from patients telling us that they can’t take part in a trial because it requires them to go into hospital every two days, which simply isn’t feasible for them. Insight like that is obvious to a patient but may not be to the pharma company designing the trial. Building these considerations in from the very start can help to improve enrolment and retention and increase the likelihood of the trial’s success.

Are there many opportunities for patients to get involved in this kind of research?

CF Europe established the Patient Organisations Research Group (PORG), which brings together national patient associations from eight countries (Belgium, the Netherlands, France, the UK, Germany, Luxembourg, Switzerland and Italy) who are actively involved in research and research funding. PORG takes a proactive approach to research to ensure that the voices of patients and their families are heard by a range of stakeholders.

We do this by collaborating with other organisations such as the European Cystic Fibrosis Society (ECFS) and organising research conferences such as our Young Investigators’ Meeting. Research should be patient-centred and patient-led, and only by collaborating with as many stakeholders as possible can this be achieved.

Is cystic fibrosis prioritised enough on the European health research agenda?

CF is the most common rare diseases in Europe, but it is nonetheless a rare disease. It can therefore be challenging to keep it on the agenda and to make people understand why it is important to address even though it doesn’t have as big a patient population as something like cancer or diabetes, for instance.

CF Europe works hard to raise the profile of CF among policy and decision makers as well as companies and researchers. We aim to highlight that it isn’t just CF patients who could benefit from CF research; other rare disease patient groups would also benefit from a greater awareness of rare diseases and increased funding for this often-neglected area.

Recently, there have been signs that Europe is working to increase its evidence base on rare diseases and prioritise rare disease knowledge and expertise. A good example of this is the creation of European Reference Networks (ERNs) for rare diseases in 2017.

These act as virtual networks in which healthcare providers across Europe can come together to discuss complex or rare diseases and conditions that require highly specialised treatment and concentrated knowledge and resources. These are especially useful because some rare diseases may have as few as ten patients in one country, and access to specialist doctors can be scattered or severely limited.

What are your hopes for the inclusion of cystic fibrosis in the upcoming ninth EU research and innovation framework programme Horizon Europe?

We need to keep in mind that CF is a rare disease and as such be realistic about our expectations. That said, there is no reason that CF should not be mentioned in Horizon Europe. Together with EURORDIS-Rare Diseases Europe, we are working to put and keep rare diseases on the agenda and in the framework programmes.

With this in mind, something I saw in the plans for Horizon Europe was a focus on bridging the East-West divide, which CF Europe has been committed to since its inception. There are huge discrepancies in CF care between Eastern and Western European countries, so that provides an excellent opportunity for us to work on access to optimal care for all EU citizens.

We also believe there is a place for CF research in the framework programme’s ambition to foster bigger and more competitive companies and support innovation, as well as in its commitment to investigator-led basic science.

How does CF Europe work to promote investment and progress in cystic fibrosis research?

The PORG is central to our efforts to promote investment and progress in CF research. Some of its main activities at present include:

  • Working on patient priorities in research and how to involve patients in the research process (both basic and clinical)
  • Collaborating with the ECFS on two important initiatives (which CF Europe also financially supports via the PORG members):
    • The ECFS Patient Registry, which collects patient data of value to CF clinical caregivers and researchers
    • The Clinical Trial Network (CTN), a network of 43 large and experienced CF centres located in 15 different European countries that work together to facilitate clinical research so that new medicines are brought to patients as quickly as possible. In particular, the CTN co-ordinates the review of new clinical trial protocols by expert groups of CF doctors, research co-ordinators, academic researchers and CF patients and their families
  • Organising, together with the ECFS, the European Young Investigators Meeting, which gives 40 young researchers (under the age of 40) the opportunity to give a ten-minute presentation on their research in the presence of their peers and leading scientists working in the field. By dedicating large time periods to networking, the meeting is intended to create a European CF young investigator community fit to face tomorrow’s challenges. CF Europe has been doing this for over ten years now
  • Organising an annual pre-conference meeting prior to the ECFS Basic Science Conference, which is designed to highlight a research topic of particular importance to CF patients. This year’s topic will be ‘CFTR: new insights on structure and function, and implications for modulation’.

CF Europe is also involved in several Horizon 2020 projects, e.g. HIT-CF Europe. It is important for us to support this kind of research and to be present in these consortia in order to represent the interests of patients and to encourage a close relationship between the patient community and researchers. It is also a good way for us to ensure that the patient is at the centre of the research and that all research outputs are communicated back to the patients and their families. Having this information helps make it possible for them to get and stay involved in different kinds of research.

Finally, close to two years ago CF Europe set up the Community Advisory Board (CAB), a group of patients who we have trained to represent the CF patient community in discussions with other stakeholders. The purpose of the CAB is to provide valuable feedback to, for instance, pharma companies on trial protocols or access to medicines and collaborate from the very early stages of the research process in order to ensure that the patient’s perspective remains at the heart of CF research.


  2. Hollin et al. Beyond the expected: identifying broad research priorities of researchers and the cystic fibrosis community, Journal of Cystic Fibrosis

Hilde De Keyser
Head of Engagement
CF Europe

Please note, this article will appear in issue 9 of Health Europa Quarterly, which will be available to read in April 2019.

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