Precision Medicines - Why?

Precision medicine is the talk of today, with a cancer drugs fund for Wales in the news and our own 'Stopping The Clock' campaign launching, calling for fair and prompt access to precision medicine for people with cystic fibrosis.

But what is 'precision medicine' and why does it matter? Dr Janet Allen, Director of Strategic Innovation, digs deeper.

On 20 January 2015, President Obama made this announcement in his State of the Union address to the US nation: 

“Tonight, I’m launching a new Precision Medicine Initiative to bring us closer to curing diseases like cancer and diabetes – and to give all of us access to the personalised information we need to keep ourselves and our families healthier.”

This was an exciting, bold statement that frames the future of treatments where individuals are treated as individuals. Recently Francis Collins, Director of the USA National Institute of Health, gave his vision of how this will be delivered, at the Faster Cures conference at the Milken Institute (pictured). He described the programme as “big, hairy and audacious – and so it should be.” 

Dr Collins argued that the time is right to do this mainly as a result of technologies coming together that will be able to inform treatments; for example genomics, environmental effects, personal wearable sensor technology. In the past, new treatments were approved based on the law of averages. For instance, how does this treatment lower the average person’s cholesterol compared to no treatment?

We need to move away from this to a state where the right drug is given to the right patient at the right time to achieve the right effect. 

This is the aim of precision medicine; we need to convert our thinking on how to keep people healthy and not see healthcare as only having a role in treating ill-health. A key component in the development of precision medicine is to engage with people as equal partners and not as subjects for study. This thinking will transform the way we do scientific research and is already creating the concept of ‘citizen scientists’. All of this will not happen overnight but the very mention of precision medicine in the State of the Union address creates momentum and it is clear that the National Institutes of Health are up for the challenge and ready. 

If you think that precision medicine is only for the ‘big’ conditions such as heart disease and cancer, see the extended quote from the State of the Union address: “21^st century businesses will rely on American science, technology, research and development. I want the country that eliminated polio and mapped the human genome to lead a new era of medicine – one that delivers the right treatment at the right time. In some patients with cystic fibrosis, this approach has reversed a disease once thought unstoppable.” 

These are truly interesting and exciting times and we need to ensure that cystic fibrosis remains in the vanguard of developing precision medicine to benefit each and every individual with the condition. This is audacious but that shouldn’t stop us. As another speaker said:

·         Don’t let perfection be the enemy of good.

·         Don’t be afraid of getting started.

·         Don’t be afraid to learn.

Find out more about our 'Stopping The Clock' campaign at www.cysticfibrosis.org.uk/stopping.

Gene editing: a therapy with masses of potential, but not only in treating cancer…

Last week gene editing hit the news with the story of young leukaemia patient Layla and a pioneering treatment at Great Ormond Street. Here Dr Anoushka de Almeida, Head of Research at the Cystic Fibrosis Trust, talks about the science behind the story, and the ground-breaking work being funded by the Trust into using genetic editing for treating cystic fibrosis.

We have recently heard on the media of clinicians at Great Ormond Street Hospital using the revolutionary technique of gene editing to treat a little girl, Layla, diagnosed with an aggressive cancer of the bone marrow. All other conventional treatments failed and this was Layla and her family’s last hope – and it seems to have worked.

So what did they do to produce such a miracle? Layla’s doctors teamed up with researchers at UCL, led by Prof Waseem Qasim, who has developed a novel approach to gene editing in immune cells (T-cells). This approach involves taking donated T-cells from a healthy person, modifying the genome using gene editing to enable them to attack cancer cells, and then introducing them into the body. Previously, these cells had only been tested in mice, so Layla was the first human to receive them. The  gene editing technique they used involved using a pair of 'molecular scissors’, a kind known as TALEN proteins, to ‘switch off’ certain receptors, making sure that the modified T-cells leave the healthy cells alone and only attack leukaemia cells. Genes were also edited out to make the new cells ‘invisible’, so that they wouldn't be destroyed by other leukaemia drugs.

 

It is still early to say whether Layla has been completely cured. The pharma company Cellectis, who collaborated with Qasim, plans to start full clinical trials early in 2016, the results of which will hopefully confirm that this isn’t just a one-off. If they are successful, this is a huge step forward for treating leukaemia and other cancers, as well as other conditions…

This leads me on to talking about the research that’s currently underway using gene editing in cystic fibrosis…

As we know, cystic fibrosis is caused when there are mutations in both copies of the CFTR gene. Recent studies have shown that the most common CF-causing mutation, F508del, can be corrected using a gene editing technique called ‘CRISPR/Cas9’ (a different method to what they used for Layla – but principally the same). The first step in this technique is to cut out the dodgy bit of genome using the ‘molecular scissor’ complex, and the second step is to repair it by using a donor DNA molecule containing the correct, non-faulty sequence. Now, this all works well in isolated cells outside the body, but the efficiency of the repair is very low. Also, difficulty arises when delivering both the molecular scissor complex and the donor DNA into the correct place in the body.

A different approach is being investigated by Dr Patrick Harrison and colleagues at University College Cork. This work, which the Cystic Fibrosis Trust is co-funding with the Cystic Fibrosis Foundation in the US, involves focusing on a small group of three rare CF-causing mutations. (These mutations basically disrupt the processing of the messenger RNA molecule which is normally needed to make the CFTR protein in cells). In all three cases, there is an extra sequence in the genome which interferes with the normal processing. Dr Harrison’s team is exploring using the gene editing approach simply to cut out this extra piece in the genome region that causes the problem. This CRISPR ‘knock-out’ strategy is more efficient than repair, and only requires delivery of just the molecular scissor complex; no donor DNA is required.

Dr Harrison’s group has teamed up with groups in Europe and the US to take this work further so that they can determine if all this hard work eventually leads to the normal CFTR protein being produced, resulting in normal functioning of the particular lung cells in cystic fibrosis.

So, off the back of the break-through in little Layla, gene editing has re-entered the limelight. It can be safely said that it is not only a promising prospect for cancer such as leukaemia, as her case unquestioningly demonstrates, but also for genetic conditions like cystic fibrosis. The Cystic Fibrosis Trust is fully supportive of this therapy and sees its exciting potential, and we would be keen to engage in further cutting-edge research in this area of genetic therapies.

 

 

 

 

 

 

Reflections on the Disability Discrimination Act

To mark this week's celebrations of the Disability Discrimination Act, our Policy Manager Nick Medhurst looks at what this has meant for those with cystic fibrosis.

It is 20 years ago this week that the Disability Discrimination Act 1995 was brought into law in the UK and it is being celebrated today as a watershed moment for equality.

It marks a moment in time when we, as a society, recognised our collective responsibility to actively support people who deal with daily challenges from a health condition or disability to achieve their ambitions.

The change in the law that it brought about, now covered by the Equality Act 2010, meant that for the first time people could request, and legally expect, for reasonable adjustments and arrangements to be made for them at work and in wider society to overcome barriers and maximise their potential.

So what has this meant for people with cystic fibrosis?

We recently surveyed 1426 people from our community about cystic fibrosis, their treatments, and what matters to them – perhaps you took part – and we are very humbled by the response we got and excited to share our findings with those who took part in the coming weeks and use those results, in every way we can, to make a positive difference to people’s lives.

One message that we received loud and clear was that managing cystic fibrosis is time-consuming (sometimes all-consuming), disruptive and sometimes impossible to balance with leading the lives that we hope for.

When fighting to keep as well as possible, people with cystic fibrosis will face hundreds and thousands of small challenges every week.

The Equality Act describes a disability as a physical or mental impairment that has a ‘substantial’ and ‘long-term’ negative effect on your ability to do normal daily activities

However, when most people hear the words ‘disability’ or ‘disabled’, I can’t imagine the image of someone with cystic fibrosis immediately pops into their head.

That seems to work both ways and many people with cystic fibrosis don’t always see the fit either. I’ve even heard that some people, likely eligible, choose not to apply for Disability Living Allowance (DLA) because they do not feel ‘disabled’.

The power of the Equality Act, and its predecessor, the DDA, is that it does not label us. It protects us, supports us and empowers us, when we can be at our most vulnerable.

For people with cystic fibrosis, it should be celebrated for the recognition it gives that people who face such challenges in their daily lives can achieve so much more if they live in a society which recognises and acts on unnecessary barriers to fulfilling ambitions.

However, we recognise that people with cystic fibrosis can and do still face discrimination and we would be interested in hearing about any challenges you have faced.