The science behind the development of the new generation of medicines

Dr Janet Allen, CF Trust Director of Research, explains the science behind the development of the new generation of medicines targeting the basic defect in cystic fibrosis.

Exciting new work presented at the NACFC reveals the science behind the search for more effective drugs to treat the commonest genetic mutation in cystic fibrosis (F508del). 

The CF gene provides instructions for making a protein called CFTR (cystic fibrosis transmembrane conductance regulator). This protein controls the movement of salt and water in and out of the cells within the body.

Depending on which mutation is present in the gene, the CFTR protein is either missing or doesn’t work properly. In those with the F508del mutation, the CFTR protein is misshapen and the body removes it (the protein must fold into very complex shapes to work in cells and act as a channel.)  So, CFTR is effectively absent in this mutation.

At the meeting today, scientists showed that the F508del mutation affects the folding of the protein through two separate mechanisms and both need to be corrected to allow the channel to fold correctly.  This detailed understanding of the basic mechanisms of the folding pathway permits the development of sophisticated new ways to search for drugs that will be more effective in correcting it. 

This study shows the critical role that basic science has in generating the next generation of drugs.

Let's mention the K word!

Ed's second blog from the NACFC

There's one word on the lips of most people here at the North American CF conference. It is Kalydeco - or, to give it its scientific name, ivacaftor.

The CF Foundation - our sister organisation in the States - describe it as "a game-changer" as it's the first CF drug that addresses the basic genetic defect.

As we know, Kalydeco is effective for those with the G551D mutation - about 4 per cent of the UK CF population - and we are calling on Vertex, the drug's manufacturer, and the NHS to do the right thing and ensure all those who need it receive it as soon as possible.

If you haven't already, help us put pressure on both by signing up to our petition here which we will present before their meeting on 22 October.

We met representatives of Vertex in Orlando today to reinforce this message, and they assured me that they would do everything they could to achieve this outcome. The Trust and the CF community expect nothing less.

Vertex also used today to present to the conference new findings from the clinical trials they have conducted on a drug to treat those with the F508del mutation, the most common form of CF in the UK and worldwide, Vertex have published data about this on Vertex’s website.

The drug is a combination of Kalydeco and a substance called VX-809, and Phase II trials in the US have shown significant impact on lung function for those with two copies of the gene.

Larger Phase III trials are due to begin early next year, and it is likely that UK patients will be included. Vertex are also doing further Phase II trials to see if a higher dose of the combination drug has an impact on those with a single copy of the F508del.

And there are final trials beginning using Kalydeco on young children under 6, and on those with the R117H mutation.

These are exciting times for CF care and research. There is real potential that, for the first time in 50 years, we are on the cusp of transformational treatments for CF.

There is much to do to extend and improve the lives of all people with CF. But, together with the advances in other treatments and care, many at this conference are beginning to believe that the future will be one that few dared even hope for just a few years ago.

Elaine Gunn, CF Registry Manager blogs from NACFC

Here I am in Florida and looking forward to find out about the US Registry on cystic fibrosis and finding out if we can make any further improvements to our own registry here in the UK. At 1230 yesterday it was the US Registry Co-ordinators Meeting. 

This annual meeting is really interesting for me as it brings together all the people who are involved with all aspects of the US registry.  It is great to know that all the same queries and questions we experience in the UK are almost mirrored in the US albeit on a larger scale. 

The CFF Registry Team lead had planned an interesting programme and kicked off by giving an overview of where the US registry was up to.  Having undergone a complete overhaul in 2010 with the introduction of a new version - which was not without some problems encountered by the users - it was now working really well.

It was encouraging to see the availability of new reporting tools for centre outcomes, quality improvements and research, what a great resource and it has taken their registry to a whole new level.

There were 27,000 people with CF registered on the US registry in 2011 and their report will be available at this conference and will be published on the CFF website

There was a presentation on data entry queries and a new initiative around patient outcomes and an audit programme to ensure high quality data was being entered. 

The session finished with a mention of the UK US collaboration work which we are involved in. We are looking at different comparisons between the two countries.  Some of this work is to be presented later on in the conference – watch this space!

Ed’s Blog – from NACFC - 11 October

So the 26th North American CF conference is underway.

It's being held in a vast conference centre in Orlando - and brings together 4,000 clinicians, researchers and others to hear the latest advances CF research and clinical care.

It’s hot here - but I don't want you to think we are seeing much of it. There are loads of important workshops to attend and people to see.

I am blogging from a meeting sharing ideas from CF centres in the US to improve health outcomes for those with CF. Some great ideas around improving adherence to treatment and targeted work focused on those who are showing a decline in lung function.

We have just heard a presentation from our own Great Ormond Street, about their "Frequent Flier" research programme. This explores how more intensive exercise can help improve outcomes for sickest children. The work showed promising results and shows how important regular exercise is to improve wellbeing of people with CF. I am very keen to explore how we, the Trust, can help encourage all individuals and families touched by CF to put exercise at the heart of their treatment regime.

One of the key issues that keeps coming up in introducing methods to improve the quality of clinical care, is the importance of involving patients and families in shaping them. This is vital, and what should be at the heart of any changes being made by CF centres in the UK.

Of course, people with CF are the key group that are not present at this conference because of cross-infection policy, but patient feed back is absolutely crucial.

I hope our blogs over the next few days can help make up something of this gap!

George Jenkins OBE, New Chair of CF Trust

Hello! My name is George and I wanted to introduce myself and and tell you a bit about me and my commitments to the charity.


My connection to Cystic Fibrosis is very personal. My son Adam had Cystic Fibrosis and sadly passed away in 1995, so I know how important the CF Trust is in securing a better and longer life for people with CF. As a CF parent I know only too well of the huge impact this has on the whole family, the extended family and our very way of life is different to others.


It is those thoughts that will be in my mind everyday as we work at the CF Trust for real improvements in living with CF.


I am absolutely passionate about the CF Trust and know that the work it does gives people with CF hope now and for the future. The impact on improving standards in Clinical Care has been great, ensuring patients have the care they should rightly receive and has meant so much to those affected by CF.


My background in business and then more recently as Chair of various NHS Trusts means that I have a good knowledge and experience of how highly the charity is regarded by clinicians, but also understand the challenges it faces in achieving the very best standards of care across all of the UK’s CF Centres and specialist wards. I am also excited by the research the CF Trust is currently funding: advances in medicines to treat CF can have an amazing impact on children and adults with CF.


I am looking forward to pushing the Trust's Living Longer, Living Better strategy and making sure it's positive financial position continues to grow and build. I'll be writing this blog regularly to give you updates on how things are going here and all the successes we have achieved.


In the meantime for those of us having a break over the summer, I hope we manage to escape the British weather and have a good summer holiday.

Best wishes


George

Message from Ed Owen

It's my second day as the new chief exec of the CF Trust, and I confess I couldn't wait to get back into the office this morning!

I have been involved with the Trust for almost ten years. I am a CF parent and have been a trustee for the last few years. So it's not entirely new territory for me. The job is an extraordinary privilege, and I am determined to ensure the Trust is doing all it can to improve the lives of those with Cystic Fibrosis.

There is much that those of us connected with the Trust can be proud of - the investment in gene therapy now in clinical trials, the fantastic work to raise standards in clinics, the vital information and support we give to families, and the wider activities to raise awareness of CF. Yet there is so much more to do.

That's why we have a new strategy - "Living longer, living better" - which sets our guiding vision for the next few years. My task is to ensure we deliver it. So we will soon be outlining a new vision for CF research and we have ambitious plans to boost our fundraising and communications efforts too.

It's an exciting time and one which needs all parts of our CF community - those with CF, their families, supporters, clinicians, researchers, trustees and staff - to work together for a common purpose. I hope I can do my bit to make that happen.

All the best

Ed
www.cftrust.org.uk

If I get my transplant I am hoping to do as much charity work as possible.

Hello, I'm Kerry Thorpe and I'm one of the faces of CF week!

I am 21 and I have 'end-stage CF' meaning I need a double-lung transplant to survive. My life is endless treatments, pain meds, IV antibiotics, I'm on 24/7 oxygen and I require a wheelchair as I get too exhausted when walking, I also struggle to climb stairs and do simple tasks such as showering and getting dressed.

Recently I've been extremely unwell, I've been on IV's since October with very few breaks, I have had 2 lung collapses requiring chest drains and then a 3rd smaller one, which thankfully didn't need a drain but it is ongoing and I still have the collapse today.
   
Due to this I can't do anything big for www.cfweek.org.uk but I am raising awareness from my living room!

In the past year I've dedicated myself to raising awareness and money for CF, my family and friends all abseiled down a building raising over £3,000, I was guest of honour at a press ball which raised £15,000 for 3 charities, the main one being CF. A good friend of mine held a ball for her birthday and all 'presents' were to be donations to CF. Also another friend is holding a party in July, all money raised through tickets etc will go to CF Trust.

If I do get my transplant I am hoping to do as much charity work as possible, I'd love to skydive or take part in a bike ride. I would also love to run the marathon, but I will start small and work up!

I hope you have a great week and manage to raise lots of money (and awareness) for CF.

Also if you haven't, please consider signing the donor register - you could save lives. www.organdonation.nhs.uk.

Thank You!
Kerry x