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Research that leaves no-one behind

With over 2,000 known mutations of the cystic fibrosis (CF) gene, CF affects everyone with the condition differently. At the Cystic Fibrosis Trust we’re committed to finding the most effective ways of treating everyone with CF, including those who won’t benefit from the ‘CFTR modulators’ currently available. Find out what progress has been made so far.

In September we marked the 30th anniversary of the discovery of CFTR, the gene that is faulty in people with cystic fibrosis. There are many places along the CFTR gene that become damaged in cystic fibrosis. Since 2013, CF clinicians have been able to offer emerging CFTR modulators like Kalydeco, which correct the CF protein, but they don’t work for everyone and there’s room for improvement in the drugs that are already available.

To address this there’s an international workforce of researchers and doctors with a wide range of expertise working to create new and better treatments for cystic fibrosis. They’re looking at it from all bases, from making the CFTR protein work better or repairing the CF gene itself to finding alternative ways to do the job of the CF protein. We’ve outlined some of them below.

Innovative drug screening for people with rare CF mutations

The ‘Human Individualized Treatment for CF’ research study, known as ‘HIT-CF’ offers an efficient way of testing CFTR modulators for beneficial effects for as many rare genotypes as possible, using cutting-edge technology. The aim is to explore the potential for the current CFTR modulators to work for rarer genotypes that they haven’t been tested against before. People with these rarer genotypes haven’t been eligible to take part in clinical trials so far.

Each participant donates a rectal biopsy sample that will be used to test all of the current CFTR modulators in the lab. In the second part of the study any of the drug combinations that show promise for a particular rare genotype will be tested in people with that genotype in a clinical trial. Drugs being tested include CFTR modulators from both Vertex Pharmaceuticals and companies like Proteostasis and AbbVie whose drugs are still in development.

Find out if you could take part in this study.

We hope that clinical trials for disease modifying treatments suitable for anyone with CF, irrespective of their genotype, will be opening for recruitment in a year to eighteen months. Sign up to the clinical trials newsletter , to keep up to date with their progress.

Making the CFTR protein work better

Thirty years on from the discovery of the CFTR gene, we know the effects some of the mutations in the gene have on the function of the CF protein, and we’ve got some effective drugs for correcting these faults, namely Kalydeco, Orkambi, Symkevi and the triple combination therapy known as Trikafta in the USA. However, researchers have not become complacent. Lab-based researchers around the world are continuing to study the function of the CFTR protein in detail.

This includes Professor David Sheppard’s lab in Bristol. Professor Sheppard is leading our Strategic Research Centre focussing on CFTR, and you can learn more about his research by watching PhD student Bartholomew Harvey’s entertaining Harry Potter-themed presentation from UKCFC (from 16 minutes in). You can also sign up to our Clinical Trials Newsletter to be among the first to hear when trials of new CFTR modulators begin.

Repairing the gene

Genetic approaches to treating CF are being explored by CF researchers across the world and one of these approaches is gene editing. It is an area that has been rapidly developing since 2012 when researchers showed it was possible to direct a pair of ‘genetic scissors’ to specific genes within our DNA using a system called CRISPR/Cas9.

Professor Steve Hart is leading a Strategic Research Centre to develop ways of correcting the faulty CF gene using gene editing techniques. If his team’s research is successful, future gene editing treatments for CF could either do ‘on the job’ repairs to the cells that line the surface of the lungs, or the CF gene could be edited in cells in the lab and then corrected cells could be delivered back into the lungs.

Good progress is being made towards genetic-based treatments. While these are unlikely to be available as standard to people with CF for many years, if they become available, they could make a significant difference to everyone.

Taking an alternative route

Rather than sitting in traffic waiting to get through roadworks, wouldn’t you rather take a diversion?! A similarly lateral approach is being explored for the treatment of cystic fibrosis. Rather than repairing the CFTR protein itself, research is underway to see if alternative proteins can be either activated or blocked to compensate for the lack of working CFTR.

Dr Mike Gray and colleagues in a Trust-funded Strategic Research Centre are looking for drugs that act on ‘alternative chloride channels’ and how these channels might work. The same approach is being investigated by the British biotech company Enterprise Therapeutics, which hopes to begin early clinical trials of its alternative chloride channel blocker in 2020.

The best thing about treatments that work on alternative chloride channels? They would benefit everyone with CF regardless of their genotype.

To find out more about trials you could take part in, including those investigating restoring CFTR function, please look at our Trials Tracker. Remember, you can use the filters on the left of the screen to choose which trials you are interested in!

Researchers are working hard to ensure that no one with CF is left behind as more treatments are developed - please donate today to support research like this.

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