Thursday, 26 March 2015

Things I learned on a summer studentship

Kate Ryan, an undergraduate medical student at Keele University, took part in the Cystic Fibrosis Trust’s Summer Studentships programme in 2014, where she worked on a PhD project on cystic fibrosis-related diabetes. Following her placement in the academic holidays, Kate won first prize for her poster presentation at the UK CF Conference.

Initially I wanted to complete a studentship over the summer as I have been interested in research ever since my first year of medical school. I gained a lot from participating in a summer project funded by the Cystic Fibrosis Trust with regards to lab skills, working as part of a team and becoming more familiar with the process of research; from planning, right through to results and presentation.

This particular project allowed me to present at my first conference which was a great experience for someone considering a career in research and helped me recognise areas I did well in as well as those I could have improved on. I also got the opportunity to meet some of the top names in cystic fibrosis research and to attend workshops about exciting new treatment options. 

Although I have had some experience in medical school, working in a lab was a relatively new experience for me. I was taught about general lab safety as well as the relevant techniques needed for my project. This hands-on approach to research was the part I found most enjoyable.

This research project has led me to consider intercalating next year and possibly considering further research in my career. It has helped me realise the importance of research and how enjoyable it can be.

I would highly recommend this to any medical student, whether you are interested in a career in research or not.

Thanks to the Cystic Fibrosis Trust for such a great opportunity last summer!

Find out more about the studentships programme at

Monday, 23 March 2015

Understanding the VX-661 Phase 2b Results

Pharmaceutical company Vertex, today released the results of a recent Phase 2b trial, which looked at safety of a drug known as VX-661 in combination with ivacaftor (Kalydeco). There has been a lot of anticipation about these results because it is only the second time that the company has issued trial data. Below, Dr Anoushka de Almeida-Carragher, Senior Research Manager looks a what they tell us.

This study involved 39 people with cystic fibrosis who have two copies of the F508del mutation, and confirmed that the treatment is safe and well tolerated.  The stated improvement in lung function, from baseline, within four weeks of treatment is also encouraging. It should be noted that the number of people who took part in the study is extremely small. However the results provide solid support for the next stage of trials – Phase 3 – which Vertex commenced in the early part of this year.

This program of four Phase 3 clinical trials will look at lung function after the administration of the VX-661/ivacaftor combination, but this time involves not only people with two copies of the F508del mutation – who were studied in the phase 2b trial, and make up roughly 51% of the CF population – but also includes people who have one copy of the F508del mutation and a second mutation that is either a gating mutation, residual function mutation or a mutation that results in minimal CFTR function.

This will the first time that the efficacy of this drug regime is being tested in a large population of people with cystic fibrosis (approximately 1150, aged 12 and older). Furthermore, the fact that 4 different ‘mutation combinations’ are being investigated, thus impacting on a larger number of CF patients, means this next-stage trial is vital in enhancing our knowledge-base in striving to reach our goal of beating CF for good.

The Trust will be watching the Phase 3 trials with interest and ensure that our CF community remain updated on the progress in transformational treatments.

Friday, 6 March 2015

Working with Pharma. Ed Owen's US blog part 2

As well as meeting the Cystic Fibrosis Foundation in the US last week, the Trust’s Chief Executive, Ed Owen, and Director of Research & Care, Dr Janet Allen, also dropped in on two pharmaceutical companies of importance to cystic fibrosis, Novartis and Vertex. Here is Ed’s second blog explaining what they find out:

Much is said about the pharmaceutical industry. Some of it is fair, some less so. But the fact remains that only pharma companies have the size, expertise and capability to develop and produce the drugs that can make a difference to people with cystic fibrosis. So it is vital that we have strong relationships with key companies, like Vertex and Novartis, and work with them for the benefit of our community. 

The Vertex story is an extraordinary one, and one in which our sister charity, the Cystic Fibrosis Foundation (CFF), has played a central role. It also tells us much about the industry, its weaknesses and strengths, limitations and potential.

Long frustrated by the lack of industry interest in cystic fibrosis in the late 1990s and early 2000s, the CFF began funding a number of commercial programmes, including one led by a biotech company called Aurora Sciences, later bought by Vertex, to find compounds to develop drugs to tackle the genetic causes of cystic fibrosis.

A decade and a half on, and Vertex is a pharmaceutical trailblazer. Ivacaftor (Kalydeco), is transforming the lives of those with the G551D mutation and a combination therapy of ivacaftor and lumacaftor has been submitted for approval for use in people with two copies of the F508del mutation.

Being a trailblazer however comes at a price, and the high price of ivacaftor has been controversial – with many questions about the likely price of the combination therapy if it is granted approval from the regulators.

With a cash-strapped NHS, and a system of drug appraisal that in England, at least, is ill-suited to assess particular issues relevant to conditions like cystic fibrosis, there is a real risk that this combination therapy is given regulatory approval in Europe later this year for use in four out of 10 people with cystic fibrosis but will not reach those that need it here in the UK for a considerable amount of time, if at all.

Our focus must be to ensure that approved therapies get to those who need them as quickly as possible - and we are discussing these issues now with all key players.

But, when we met them last week, Vertex continued to be tight-lipped about future pricing in advance of regulatory approval. Along with other pharmaceutical companies, the company argues that the price of drugs reflects both the high cost of investment that has been made over many years to develop and trial therapies (estimates vary, but the average cost of producing a new drug is usually well above £1bn) and the relatively small numbers of patients with ‘rare diseases’ like cystic fibrosis.

Like every other pharmaceutical company, Vertex has shareholders who demand an appropriate financial return on their investment. The long-term prospects of the cystic fibrosis ‘market’ means that Vertex is continuing to invest in both their immediate pipeline of potential therapies and in longer-term research to develop what they describe as ‘second generation’ drugs that they believe could be even more effective in future years.

We are delighted they are doing so, and are keen to see other drugs companies invest in cystic fibrosis research too. One such company is Novartis. It already produces cystic fibrosis drugs, most commonly Tobramycin. But we have had concerns about its future commitment following its decision to move its wider respiratory research base from Sussex in the UK to Boston in the US in late 2013.

We were therefore pleased to meet the Novartis team in Boston last week and to receive their reassurance that their cystic fibrosis-related drug programmes were alive and well.

For the first time in decades, the pharmaceutical industry is investing heavily in cystic fibrosis. As President Obama said in January, the condition is at the cutting edge of new advances in ‘precision medicine’ with new therapies being developed focused on defined patient groups with particular genetic mutations.

That investment will only continue for as long as companies believe that health systems will pay for the drugs that follow. Therein lies the challenge for the NHS, ourselves and all those wishing to see innovative treatments that transform the lives of people with cystic fibrosis accelerated as quickly as possible.

High-cost drugs are the future. How they are paid for is the key question that we all need to address. 

Saturday, 28 February 2015

My successful SRC grant application

As the Cystic Fibrosis Trust announces a call for applications to form up to three more Strategic Research Centres, Dr David Sheppard of the University of Bristol explains how he went about submitting a successful SRC application.

As a scientist based at a UK university, a significant part of my time is spent applying for research funding. This funding provides salaries and bursaries for the research fellows and students that I have the privilege to work with. These highly creative individuals labour for long hours in the lab to understand better how the cystic fibrosis transmembrane conductance regulator (CFTR) works, how it goes wrong in cystic fibrosis (CF) and how drugs repair the faulty CFTR. Funding also covers the cost of all the “stuff” required to do experiments in the lab. In our case, this involves some very expensive equipment needed to monitor CFTR activity as tiny electrical currents, paraphernalia to grow cells and a battery of chemicals to stimulate CFTR and manipulate its activity. Simply put, without funding there is no research.

With my research focusing on CFTR, the CF Trust is the major funder of our work. I’m extremely grateful to the Trust for the funding that I have received over the last 20 years. The output of our research has included knowledge of how gating mutations (eg, G551D) interfere with CFTR function and the action of chemicals that act as CFTR potentiators. This information has helped the development of transformational drugs that treat the root cause of CF.

When the CF Trust announced its new research strategy in April 2013, I began to think about how to apply for a Strategic Research Centre (SRC) grant from the Trust. SRCs are virtual research centres of excellence that bring together research groups from the UK and overseas to tackle a fundamental problem in CF.

What problem to address? Great progress has been made in our understanding of F508del, the most common CF mutation, leading to clinical trials of CFTR correctors and potentiators. While very encouraging, data from the lab and clinic argue that better drugs are required to fully rescue F508del-CFTR. By focusing on F508del-CFTR, the SRC would have the potential to benefit the largest number of individuals living with CF.

Today, most research is multidisciplinary, meaning that methods from different research disciplines (eg, biochemistry and physiology) are used together to solve specific questions. While some labs successfully apply different research methods, many specialise. My own work is very highly specialised, focusing on how individual CFTR proteins work. To apply successfully for SRC funding, we would need to collaborate actively with other groups expert in studying CFTR structure, how it is made inside cells and delivered to its correct cellular location. We would also need help from pharmacologists expert in testing large numbers of chemicals for drug action.

Early in planning the application, I approached Professor Bob Ford from the University of Manchester. Bob has been at the forefront of efforts to identify the structure of CFTR. This work is fundamental to understand CFTR and its dysfunction in CF. I also approached Professor Ineke Braakman from Utrecht University in The Netherlands. Ineke and I had previously made plans to study how CFTR matures inside cells to become a gated pathway for chloride movement. When compared with other methods to study CFTR activity, those used by my Bristol colleagues are notoriously slow. Two groups studying CFTR activity would therefore be advantageous for an SRC application. Because of her expertise in studying how CFTR flutters open and closed, I approached Dr Paola Vergani at University College London. I was delighted that Bob, Ineke and Paola all readily agreed to participate in the SRC application.

Plans for the SRC were finalised at a conference in Malta organised by the European CF Society last March. Because the meeting was so intense, it was not until the day after the meeting that Bob and I finally found time to discuss, in detail, plans for the SRC, especially how the different project partners would work together to address our research goals. During these discussions, we recognised that the SRC would require a group expert in the pharmacology of CFTR. With his wide-ranging expertise in studies of drugs targeting CFTR, we both agreed that Professor Frédéric Becq from Poitiers University in France was an excellent choice. Returning to Bristol, I telephoned Frédéric to invite him to join; he agreed immediately. With the team recruited, we then set about writing the application. The initial application went smoothly, but the full application involved a lot more work; not for the first time lots of late nights and early mornings close to the deadline!

Bob, Ineke, Paola, Frédéric and I were delighted to learn that our SRC application was successful. We are excited about the studies of F508del-CFTR that we have planned. We believe strongly that they will inform the development of new drugs to benefit the majority of individuals living with CF.

Thursday, 26 February 2015

Back from Boston & Bethesda

CEO Ed Owen and Director of Research Dr Janet Allen spent the first half of this week in the US, meeting with colleagues from across the American cystic fibrosis community. Ed fill us in on some of the highlights from meeting with our US counterparts.
Weeks of sub-zero temperatures and Arctic-like weather have left much of the North Eastern coastline of the US encased in ice and snow. Yet our visit this week to see Vertex and Novartis in Boston, and the Cystic Fibrosis Foundation (CFF) in Bethesda, demonstrated that the work to beat cystic fibrosis continues to generate a great deal of heat and light.

What we heard from all those we saw gives me renewed confidence about the future prospects of research. But, while competition in the pharmaceutical industry is an important driver in pushing the development of new drugs, this needs to be matched by new forms of international collaboration and partnership that pools effort and resource in the best interests of people with cystic fibrosis.

Our strong relationship with the CFF is crucial here. We have shared goals, represent communities of people who are themselves increasingly interconnected, and both have access to key clinical, academic and business expertise. We can bring this together on tackling the big issues facing people with cystic fibrosis so the potential for greater and quicker advances becomes a reality.

The Foundation’s success in helping to develop and promote new therapies in cystic fibrosis has been extraordinary.  We in the UK owe a great debt to them – and their $3.3bn windfall late last year resulting from the selling of their Kalydeco royalty rights gives them significant new resource to invest in new research to bring hope to everyone with cystic fibrosis wherever they live.

But, as the Foundation will readily admit, they do not have a monopoly on wisdom or expertise – and are keen, too, to explore areas of collaboration with the Cystic Fibrosis Trust in particular areas that can bring impact.

At our meeting, we therefore discussed a range of areas of potential joint research activity. One was tackling the challenges posed by what are called ‘nonsense mutations’ of cystic fibrosis, and developing novel treatments that would benefit around 1,000 people here in the UK alone. The existing pipeline of small molecule therapies being developed by Vertex and other pharmaceutical companies would not affect this group so it is an important area for ourselves and the Foundation.

A further area we explored was transformational work in gene therapy and stem cell research. The UK has particular expertise here, not least that generated by the Gene Therapy Consortium, supported by the Trust over many years and soon to publish the results of its Phase 2b study. In stem cells too, the UK has a strong scientific base and we are keen to see more of this focused on cystic fibrosis over the coming years.

We also discussed joint approaches to tackling emerging infection threats to people with cystic fibrosis such as NTM and aspergillus. The CFF is supportive of the Strategic Research Centre on NTM being funded by the Trust, and keen to follow its progress.

Finally, we talked about our SmartCareCF programme and working together to harness new technology to give people with cystic fibrosis the tools to take greater control of their lives, as well as increasing access to clinical trials here in the UK.

I believe that in these and other areas we can demonstrate real collaboration over 2015 to bring together the greatest possible expertise and resource in our collective fight to beat cystic fibrosis for good

Tuesday, 24 February 2015

Moving Mountains - “Making the impossible possible with exercise”

Last Friday saw Churchill College, University of Cambridge, host the Moving Mountains conference on how sport and exercise can benefit those with long-term health conditions, such as cystic fibrosis.

Our own, Paul Rymer, Head of Principal Involvement attended from the Trust and has given us a flavour of the informative, interesting and exciting events there

In the next year fitness and sport will be an increasing focus for the Trust. Last week I attended a conference highlighting the benefits of exercise, including better mental health, less reliance on drugs, and increased feelings of confidence and social inclusion.

The event was organised by Dr Jonathan King, who has CF, in partnership with others living with chronic conditions.

Jonathan used a slide presentation and props (bottles of water) to engagingly describe lung function, his treatment regime, what happened when things went badly wrong during a holiday, and then the months of recovery. With persistence, and support from his care team, Jonathan managed to avoid a lung transplant by gradually improving his lung function though exercise. At first he could barely move, but over a period of months he gradually increased his physical activity, from walking a few steps, to trying a treadmill, to jogging and then to running 4K. Jonathan now uses regular exercise to maintain his health. His next endeavour is to cycle 1,200 miles from London to Barcelona in support of the Cystic Fibrosis Trust.

Nick Talbot gave an extremely funny account first of his experience as a young man with CF, including dating, relationships and work. He then shared his experiences climbing mountains in the Himalayas, and the challenges of doing that with cystic fibrosis. Where Jonathan’s story was one of survival against the odds, Nick’s was an example of someone not accepting the perceived limitations of cystic fibrosis. Nick is aiming to climb Everest in support of the Trust in April–May.

Charlotte Wells, a specialist respiratory physiotherapist, talked engagingly about her experience working with CF patients, and the benefits of exercise from a clinical perspective.

Because of the risk of cross-infection, Jonathan spoke before a break time, and stayed in one area of the large venue, while Nick arrived later on, and aside from when he was speaking, remained at the back of the audience. At one point they were both in the venue, but at the widest possible distance (and it was a very large theatre). They then spoke through microphones asking each other questions. This really brought home one of the saddest aspects of living with cystic fibrosis – people unable to meet in person and share ideas, jokes and experiences.

Following the conference there was a drinks reception with special guest of honour Professor Stephen Hawking, who kindly posed with Nick and a Trust banner. In a short speech, Professor Hawking said: “You have to live life to the full. I am very aware of the preciousness of time, act now however difficult life may be there is always something you can do, be brave overcome the odds, it can be done.”.

If you have an interest in exercise, fitness or sport and would like to join me in exploring how the Trust can do more in this area, please email me at

Monday, 16 February 2015

Thoughts On Stem Cell Research & Treatments

Many will have read about the story earlier this month of a young woman with cystic fibrosis, Roisin Kelleher, who travelled to the Dominican Republic in order to undergo a controversial stem cell procedure. Here, our Chief Executive, Ed Owen, reflects on the difficult issues the case raises and why the Trust cannot recommend others pursue the same course:

There’s been much interest and debate on the use of stem cells as a potential transformational therapy for cystic fibrosis in the wake of publicity around Roisin Kelleher’s story.

Roisin is 20 years old and lives in Kent. She is dependent on oxygen, has been recently diagnosed with pulmonary hypertension and has been told by her clinical team that a lung transplant is probably the only way to prolong her life. Her mum Anntoinette told me when I spoke to her this week, “our lives caved in” at the news and they were desperate to find alternative routes to bring hope for her daughter.

After undertaking a great deal of research on the internet and through other networks, Anntoinette came across the work of a Florida-based physician, Dr Zannos Grekos, who has been promoting a particular stem cell therapy for a range of debilitating conditions, including heart and lung failure. Under his procedure, patients travel to the Dominican Republic where stem cells are introduced into the body intravenously.

Roisin and Anntoinette decided to give it a chance, and raised the funds they needed to travel to the Dominican Republic and undergo the procedure. Roisin is now back home and you can read her personal story on her Facebook page, ‘Breathe Hope for Roisin’.

So what is our view of this particular therapy? It is the question we have been asked by many, including some in the same situation as Roisin who, inevitably, are asking themselves whether they too should seek to undergo this procedure as a way to bring hope of future life.

In answering this question it is important to start by saying that all of us understand the desperation felt by the Kellehers. Theirs is a heartfelt story experienced by many other families touched by cystic fibrosis – and all of us wish Roisin well over the next few weeks and months. Like every other member of the wider cystic fibrosis community, they deserve and should receive full support and love from us all.

But the Cystic Fibrosis Trust does not recommend that others follow their example because it is a procedure that has not undergone the minimum essential procedures to guarantee patient safety. Indeed, the very reason it is carried out in the Dominican Republic is because it is not authorized by the US regulators, the FDA.

I have been in contact with a number of cystic fibrosis experts in the UK and in the US over the last few days, and none believes that this procedure has any scientific or clinical basis. It should also be pointed out that, in 2013, the Florida Board of Medicine removed the medical license of Dr Grekos for committing medical malpractice in performing an “unproven” stem cell therapy on a patient who later died. The board's vote was unanimous and without discussion, although I understand he may be appealing this decision.

I admire Anntoinette’s spirit and deep love for her daughter.  She accepts their decision was a “leap of faith”, and is also keen to point out that Roisin continues to take her existing treatments and is still going through a transplant assessment here in the UK.  She also understands the position the Trust takes on this issue.

And what we all very much agree on is the need for more research into the use of stem cells in cystic fibrosis.

For all the professional scepticism about Dr Grekos’ procedure, there is a great deal of enthusiasm within scientific and clinical circles for the longer-term potential offered by stem cell research. The Cystic Fibrosis Foundation in the US is looking to invest heavily in this field  and we, too, are exploring some innovative areas of work in this area which we hope to announce soon.

This is not work that is going to bring potential clinical therapies soon, and we are some way from even early stage clinical trials. But it is a genuinely exciting area as part of our mission to beat cystic fibrosis for good, and we will not stop until we get there.

In the meantime, our hearts go out to Roisin at this time, and to all those families facing the daily battle to ensure their loved ones remain with them. You are, quite simply, our inspiration in the fight against this cruel condition.

We are continuing to look into this issue, as we do with all developments in cystic fibrosis care and research. Please do keep an eye out on the Trust’s
Facebook, Twitter and website, as well as this blog for updates.