'Designer babies' and cystic fibrosis: Where's the connection?

Our Director of Research and Care, Dr Janet Allen, takes us through the recent discussion around 'designer babies' and where cystic fibrosis fits in.

The recent media focus on ‘designer babies’ has challenged thinking about what the future could hold; using tools to correct mutations in genes such as those that cause cystic fibrosis. 

It is important to understand that the correction of mutations (also known as genetic editing) can be done in the laboratory today using CRISPR technology. In fact the Trust is already funding two programmes in this area for cystic fibrosis. At the same time, a small biotechnology company has been pioneering a slightly different approach of repair called RNA editing and is about to start on very early clinical studies. 

Gene or RNA editing are both forms of gene therapy, although different from conventional gene therapy which we have been funding through the Gene Therapy Consortium. Conventional gene therapy inserts the corrected gene into the airway cells; in the editing approach, the mutation in the person’s own gene or RNA is corrected. The big question is whether it is possible to transfer the laboratory successes and correct CF-causing mutations in people’s lungs.

These are early days and already people are thinking about the next, next generation of gene therapy, combining genetic editing with stem cells to overcome constraints on delivering the corrected gene. It is possible to take cells from a person and, in the laboratory, convert them into stem cells (called iPS) specific to that individual. The CF-causing mutation can then be edited in the laboratory and the stem cells converted back to lung cells. A Trust-funded project is just about ready to start and we should know by the end of this year whether it has been successful in the laboratory.

So what does this all mean for the designer baby debate? Well the technology to edit out the CF causing mutation is exactly the same for designer babies as the next generation and next, next generation gene therapy approaches already taking place. 

For designer babies, this editing would need to be completed in the embryo and this is where the ethical considerations become the overriding issue and it is good that we’ve been challenged to start the debate, well before any of this advances. The debate gets tricky because the same technology that could correct for conditions such as cystic fibrosis could be used for non-health issues, such as hair or skin colour that a parent deems less desirable.

In the UK, we have an excellent framework to control research activity and ensure topics like these are well-thought through and all ethical considerations given time. Legally, this area is tightly controlled by the Human Fertilisation and Embryology Act 1990. Pioneers in the UK such as Dame Mary Warnock developed the thinking and ethics that allowed IVF to start and the recent ‘three parent’ programmes for some muscular dystrophies. In many respects, through the formation of the Human Fertilisation and Embryology Authority, these pioneers have provided the framework to safely explore challenging scientific advances such as designer babies and for the UK to lead the debate and provide thought-leadership in this area. It is good to hear also that the highly respected Nuffield Council on Bioethics is also considering the matter.  

Lung function in children with cystic fibrosis: A comparison between the UK and the US

Dr Anoushka de Almeida-Carragher, Senior Research Manager at the Trust looks at the recent discussion around the differences in average lung function between CF children here in the UK and those in the US.

In September last year, a paper was published in the journal ‘Thorax’, which reported that the average lung function in children and young adults with cystic fibrosis (CF) in the US was significantly better compared with those in the UK. The study was conducted by Christopher Goss and colleagues, based in the US and the UK. They collected data from the UK and US Registries and compared CF outcomes and the use of treatments.

The results of this study have undoubtedly raised some concerns, especially among some CF researchers in the UK. One issue is the fact that the UK Registry is more representative of the whole UK CF population (who have universal access to care via the NHS), whereas the US’s Registry only captures data of patients attending accredited CF centres. As a consequence, the UK’s data may show info from more disadvantaged socio-economic groups resulting in poorer clinical outcomes, compared with the US.

The paper does not explore the reasons, in great depth, behind the difference in lung function, but it does suggest that in the UK, chronic pulmonary therapies (like sterile hypertonic saline solution which helps clear mucus from the lungs) had been used much less frequently to treat young people compared to the US. They also speculate that the difference could be due to the difference in frequency of visits to CF centres; in the US, CF is only treated at specialist centres, while in the UK, care is managed between local hospitals and specialised units, and in some parts of the UK, young patients may only visit a specialist centre as little as once a year and then visit their local hospital the rest of the time, where they may not be seen by a CF practitioner.

What we can conclude is that making comparisons between one country and another is useful and informative, especially where there are obvious differences in care and treatment methods. Even though the results of this study show a lung function discrepancy between the two countries, the explanations for such differences are not definitive. Further investigations, such as cross-country longitudinal studies using Registry data, on a like-for-like basis, are essential before we can draw conclusions between treatments and outcomes in the global CF population.

You can learn more about research into cystic fibrosis at www.cysticfibrosis.org.uk/research

Remembering Emily Thackray

Emily Thackray was a committed and enthusiastic campaigner and fundraiser for the Cystic Fibrosis Trust for many years, and sat at the very heart of the community throughout her life. Emily died on 28 December 2014 and today she will be remembered and celebrated at her funeral and wake.

This blog was written by Oli Lewington, Engagement Director at the Cystic Fibrosis Trust – a friend of Emily’s – in the days following her passing.

Lots of things will be written and spoken of Emily Thackray in the next few days and weeks. She died yesterday after a second double-lung transplant proved too much for her body to withstand.

Emily’s unique ability – using unique in its literal sense, as I’ve never come across anyone with the same gift – was to make everyone she ever came into contact with feel like they were the most important in her world.

There are dozens of people who will be grieving the loss of a best friend today, because that’s who she was to everyone: selflessly sharing her love and compassion for the world with all she brushed against and, in the process, making everyone she touched feel special, feel like they mattered. She made a difference.

Equally, everyone who knew her will have their own ‘Emily’ with whom they spent time, shared laughs and cried when it was warranted. We all knew a different friend who gave different things to our lives.

My Emily came into my life in the early days of the internet when I first discovered the Cystic Fibrosis Trust forums: she was already there and dispensing support and advice as needed. I struck up a friendship with her and with some of the other frequent posters and we supported each other through tough times of losing friends that we were terribly close to. It seems nothing much changes in a life with cystic fibrosis.

When she set up the organ donation campaign (now charity), Live Life Then Give Life, with her great friend Emma after the loss of more than one mutual friend on the waiting list for transplant, I offered to help in any way I could. I ended up being one of the first Trustees of the charity and being part of the team that one Best Campaign Team at the 2008 Charity Times Awards and Best New Charity the following year.

My Emily was always one step ahead of me on my CF journey. She was the first of us to start needing supplementary oxygen. She was the first to use a wheelchair. She was the first to have a lung collapse. She was the first to be assessed for transplant and, thank God, the first to receive it. She was the first to be married after her transplant, and the first to have serious complications. Now, she’s the first of the two of us to go.

What became indelibly unique, though, was that everything she went through became a source of help and information for others. She never hid away from anything and always used her own lived experience to make it even a tiny bit easier for others going through it. She supported me as I took every step and misstep she took, a few months further down the line.

The day I finally got my transplant call I remember sending her a message and getting an immediate phone call back.

“Take some paracetamol now,” she told me.

I wasn’t sure if I should, but she countered immediately, “The stress of the situation might raise your temp and if it does they won’t go ahead. Take two paracetamol now and it will drop your temp if you have one, but it won’t mask anything more serious that could be a real contraindication.”

I took them. I passed the tests. I got new lungs.

The story that sums up Emily, though, came through on my Facebook last night from one of my oldest friends and was one that I’d never heard before. This stands as testament not only to her willingness to help and support anyone and everyone, but also to be humble and quiet in going about it.

“She was so wonderful when you got your call, patiently, calmly keeping me informed about the stages, what to expect, what were the good signs, what to worry about & what to cheer.

“All the way through your surgery and recovery she stayed in touch, answered my many emails and sent me random messages asking how I was doing – she had volunteered herself to essentially be my support as I didn’t want to bother your parents or K too much with my need for information and updates. It meant such a lot to me and I was incredibly appreciative knowing she was a message away to answer a question or calm a worry.”

That’s Emily: friendly, warm, generous and patient. And not just my Emily, that’s everyone’s Emily.

Em, you will be missed far more than most of us can understand, but we remain ever grateful for the joy and happiness you brought to our lives, for the connections and friendships you forged that will last long into the future, and for the blessing of finally understanding one of my favourite quotes:

“She was a line of poetry in a world of prose.”Polly Toynbee

Thispost first appeared on the SmileThroughIt blog. If you would like to make a donation to the Trust in Emily’s memory, please click here.

New Medicines in Scotland

On Monday, Cayston, a new nebulised treatment to tackle Pseudomonas in people cystic fibrosis was approved for use in Scotland. Here, Yvonne Hughes, Public Affairs Officer for Scotland tells us more about how such decisions happen.

The decision this week by the Scottish Medicines Consortium (SMC) to approve another drug for cystic fibrosis underlines how the work the Cystic Fibrosis Trust does here in Scotland is making an impact. As Public Affairs Officer, ensuring access to new medicines is a part of my job that may appear a bit boring at first, but is an essential and enjoyable part of my work and allows the Trust to make the representation on behalf of the CF community.

With the help of clinical CF staff across Scotland, I am able to contact patients who are on the trial for the new drugs being assessed. It is crucial that the patient experience and that of their families is captured in papers we submit to the SMC as it could be the difference between a Yes and a No recommendation. Without your help drugs like Kalydeco and Cayston may never have got to clinics, so I am extremely grateful. I have also made a few friends in the process! As someone with cystic fibrosis I understand how isolating it is, so to speak to you and hear your stories is always a pleasure.

The recent Cayston decision fell under changes made last year to the way medicines are appraised to improve access for those at end-of-life or with a rare disease. A Patient and Clinician Engagement meeting (PACE) has been introduced where it is likely a drug may not be approved. Cayston went through this process and we found it to be valuable, particularly as we were able to talk about living with cystic fibrosis direct to people involved in making decisions around new medicines.

The changes to the SMC will be up for review this year and I shall feed in to that process but in the meantime I will continue to ensure that patients with cystic fibrosis are represented when new drugs come online. Please feel free to leave a comment or get in touch with me yvonne.hughes@cysticfibrosis.org.uk.

Newborn Screening

With newborn screening in the news, Rebecca Cosgriff, UK CF Registry Lead, looks at the difference the heel-prick has made in detecting cystic fibrosis sooner. 

2015 is off to a great start with the news that newborn screening in England will now detect more genetic diseases.  Wales will expand its newborn screening programme later this month, whilst Scotland and Northern Ireland are yet to announce a decision.

Newborn screening involves pricking the heel of a baby between five and eight days old, so that the blood sample can be tested for genetic disorders. It is important to diagnose genetic diseases as soon as possible, so that treatment can begin before organs are damaged.

Following a Cystic Fibrosis Trust campaign, newborn screening has been routinely used to detect cystic fibrosis since 2007. UK CF Registry data shows that since then the median age of diagnosis each year has dropped from five months to 30 days. The number of people diagnosed each year by the time they are three months old has increased from 46% in 2007 to 72% in 2013. During the same period the median age of death has risen from 24 to 29 years.

It’s fantastic that the example of cystic fibrosis, along with other genetic diseases already part of the programme, has paved the way for similar improvements in these new areas.

Looking Back, Moving Forward.

Ed Owen, Chief Executive of the Cystic Fibrosis Trust, looks back on our 50th anniversary and the successes of those 50 years, and how the Trust will build on them as we enter 2015 and beyond.

The Trust's 50th anniversary was never cause for celebration. How could it be when so many with cystic fibrosis can still only dream of reaching such a milestone, and when the lives of so many young people like Emily Thackray, who died this week , are so terribly cut short?

But 2014 has enabled us both to mark the contribution of all our supporters and, most importantly, to redouble our effort to beat this cruel condition for good.

The decision of HRH The Prince of Wales to take on the Patronage of the Trust this year was a fitting reward for the extraordinary commitment and dedication of all parts of the cystic fibrosis community - people with the condition, families, supporters, fundraisers, campaigners and many others .

The tireless efforts of so many over five decades has helped ensure vital research is funded, NHS care has improved and over time, turned what was exclusively a childhood disease in the 1960s into one where the majority of those with cystic fibrosis in the UK are adults.

And I want to add my tribute too. So, on behalf of all of us who work at the Cystic Fibrosis Trust, I send a massive thank you for everything you, our supporters, do on behalf of those we are here for.

Yet with so many young people dying early, and with the lives of all those affected being limited so severely by the daily physical and psychological burden of cystic fibrosis, our collective community activity, unity and voice are as critical today as they have ever been.

We are at the beginning of a new era of opportunity in the treatment and care of cystic fibrosis. Research breakthroughs offer the prospect of gene-modifying treatments for many with the condition, and new technology promises new ways of improving health and wellbeing.

2014 saw further steps forward with the continued use of Kalydeco showing extraordinary results for those with the G551D mutation, and results of Vertex's Phase III trial into its ‘combination therapy‘ focused on those with two copies of DF508. The latter is soon to be considered by European regulators with a decision likely in late 2015.

The Phase IIb trial of a gene therapy product was also completed in the summer of this year. This is the latest development of work which has been generously supported by the cystic fibrosis community in the UK over many years, and we await the results with keen anticipation.

After a short delay caused by further work processing the trial data - this is the largest research study of its kind in the world - we expect the Gene Therapy Consortium to publish the final results early in 2015.

Alongside these promising developments, the Trust has been investing in other vital research projects aimed at tackling issues of real concern to those with cystic fibrosis. Three new Strategic Research Centres were announced early in 2014 focused on vital issues like pseudomonas and NTM - and we are due to announce a further three new SRCs in early 2015 ensuring that the brightest and best scientific efforts we can find are focused on the issues that really matter.

2015 will also see the development of the Trust's SmartCareCF programme to bring industry and academic experts together with people with cystic fibrosis, their carers and clinicians to develop new forms of care using smart technology and big data.

SmartCareCF is one of a number of ambitious programmes we at the Trust are developing as part of our renewed determination to beat cystic fibrosis. These include new research projects, better support for people with cystic fibrosis and more effective ways to campaign for new drugs, tackle funding shortages in the NHS and raise wider awareness of the condition.

In order to deliver these ambitious plans we must ensure the organisation of the Trust is fit for the task. So we are making a number of internal changes including the introduction of new skills and expertise in specialist areas of fundraising, research and communications; investing in new IT and looking at new accommodation options; and bringing in new talent at trustee level to ensure the Trust is being led effectively at this important time.

We are also improving the way we communicate, support and learn from our supporters, particularly those living with cystic fibrosis - and sharpening our message to raise wider awareness and impact. 

This recent film produced for our partnership with the British Comedy Awards is an early example of how we can do so.

50 years on and, with your support, the Trust continues to play a major role in improving the lives of people with cystic fibrosis in the UK. But we must now seize the opportunity to make transformational change over the next few years. With the help of the wider community here and overseas we can and will ensure that cystic fibrosis is barely more than a distant memory when the next 50 years comes around.

A cystic fibrosis 'cure'? - Understanding this week's research news

Following recent news reports of a ‘cure’ for cystic fibrosis being within reach, Cystic Fibrosis Trust Chief Executive Ed Owen discusses the promising research at the centre of the story, and the need to think big but stay grounded.

Nothing is more guaranteed to get all of us excited than stories of a possible ‘breakthrough’ or ‘cure’ for cystic fibrosis.

So a news item on Channel Four News this week heralding a research project led by Dr Anil Mehta in Dundee as a possible cure for cystic fibrosis has understandably caused a wave of interest among many of us affected by the condition here in the UK.

In a blog on Tuesday accompanying the news piece, the veteran broadcaster Jon Snow described the research as a “Eureka moment” that offered the hope of a “cystic fibrosis cure”. Many people called our office to find out more, dozens tweeted and hundreds posted messages on Facebook at what appeared to be a remarkable moment.

So amid all the excitement, what’s the reality?

First, it is important to note that no research paper has yet been published so we at the Trust have not been able to see the detailed analysis. But the facts according to the University of Dundee’s press statement are that in an early stage clinical study undertaken in Italy, medics trialled the combined use of two drugs already licensed for other conditions - Cysteamine, and epigallocatechin gallate (EGCG) – involving 10 people with cystic fibrosis with two copies of the DF508 gene.

The University statement says that the study found that the two drugs given together reduced inflammation in 9 out of 10 of the patients’ airways and also dramatically reduced their sweat chloride levels. Obviously, then, the research looks promising. But it’s at an early stage trial and used only a very small sample.

I had the pleasure of speaking with Dr Mehta on Wednesday and he agreed with me that talk of a potential cure was misplaced. He acknowledges that his work is at an early stage but wants it to now go forward to a larger Phase 2 research study involving 120 patients. He is planning to submit an application to the Government’s Medical Research Council (MRC) which supports this kind of clinical research in the UK, although there are a number of regulatory hurdles the work needs to overcome first.

As a result of the extraordinary support we receive from thousands in our community, the Cystic Fibrosis Trust is currently investing in a wide range of research projects aimed at improving and transforming the lives of people with cystic fibrosis. This has helped fund earlier stages of Dr Mehta’s work and our new Venture and Innovation Awards created last year are targeting funds at projects like this one as a way of bringing in even larger sums of money from the Government and other quarters.

Dr Mehta and I discussed these funding arrangements and – once we have analysed the full details of this work – we stand ready to offer such an award as part of the process of bidding for MRC funds.

But, three days on from the story being broadcast, I confess to feeling disappointed at the way it was covered.

Talk of breakthroughs and cures make great headlines. But such hyperbolic coverage risks the unwitting manipulation of the emotions and passions of those of us desperate to believe that there is an imminent prospect of being freed from the terrible clutches of cystic fibrosis. Put bluntly, such stories bring into sharp focus the stark contrast between longer life and an early death.

I say this not to pour cold water on all our hopes because this particular project looks promising – and I am hugely optimistic about the wider future for cystic fibrosis. Kalydeco is already correcting the basic genetic defect of cystic fibrosis for four per cent of people with the condition in the UK – and, with the active support of the cystic fibrosis community, I believe we can help ensure that new transformative therapies and treatments will be introduced over the next decade that move us closer to our goal of beating cystic fibrosis for good for all.

But developing these drugs is expensive and often a long slog – and what might look hopeful at an early stage of development cannot be assumed to be a guaranteed success in clinical terms further down the line.

So the lesson to us all from this week is let’s keep thinking big, but with our feet on the ground – even if, sometimes, media headlines tempt us to do otherwise.