Developing effective treatments for all

Genetic therapies are a type of treatment that are being developed for cystic fibrosis. They work in a completely different way to CFTR modulator medicines. There are currently no CF genetic therapies approved as treatments. However, in the last few years, many are starting to be tested in clinical trials. 

You can read and listen to videos explaining more about genetic therapies in our genetic therapies resources section of the website, and by searching for ‘genetic therapies’ on our Trials Tracker.

Gene editing research

Gene editing approaches are a kind of genetic therapy that are currently being studied in the lab. The aim of gene editing is to repair the existing faulty CFTR gene itself, so it can make a fully-functioning CFTR protein.

Our Strategic Research Centre on therapeutic gene editing, co-funded by the Trust and the CF Foundation in the United States, is supporting researchers led by Professor Stephen Hart at UCL Great Ormond Street Institute of Child Health to investigate the design, testing and delivery of gene editing therapies for cystic fibrosis. 

Read more about our SRC on therapeutic gene editing

Researchers around the world are investigating treatment approaches for a group of rarer CF variants known as ‘Class 1’, ‘stop’ or ‘nonsense’ variants (these are all names used for one group of CF variants). People with class 1 CF variants do not make full length copies of CF protein.

We’re funding a Strategic Research Centre to support this area of research, led by Dr Mike Gray at Newcastle University. A team of researchers from across Europe are investigating potential medicines that work in two different ways to allow a full-length protein to be made. It is hoped that these new medicines would work in combination with CFTR modulator medicines. To find out about this exciting approach, read the summary of the Karen Menzies PTSuppress SRC.

Find out more

Sometimes it is very difficult to tell if someone has cystic fibrosis, especially when they have rarer CF variants. This can be difficult both during newborn screening and as symptoms of CF are explored in older children or adults. We are funding research to address these challenges.

More information on CF diagnosis can be found in the ‘How is CF diagnosed’ section of our website.

Newborn screening for CF background

The newborn screening test for CF, also known as the ‘heel prick test’, has been very successful at quickly finding out if babies have CF, but sometimes the tests can lead to uncertainty about whether or not someone definitely has CF. For some babies, a positive newborn screening result suggests that they might have CF, but follow-up tests do not confirm a diagnosis of CF. Where there is uncertainty, children may be given a designation of CFSPID (‘CF-screen positive, inconclusive diagnosis’).

 A small number of children with CFSPID may develop CF as they grow older, meaning that the majority of children with CFSPID remain well. However, it is difficult to predict whether an individual child with CFSPID will develop CF or not.

Could new lung tests help monitor children with CFSPID?

For CF teams and children with a CFSPID designation and their families, there is a difficult balancing act of monitoring the child’s health in case they go on develop symptoms that can be treated, but not checking them too much, to allow them to live with as little disruption as possible to day-to-day life. 

We’re co-funding research with the charity Action Medical Research to understand more about which children with CFSPID might be more likely to develop CF or CF-related disorders in the future. The researchers, led by Dr Rebecca Dobra, will follow the health of 25 children with a CFSPID designation over two years. They will study if the results from a new, more sensitive test of lung function and radiation-free imaging can detect those that are more likely to develop CF.

Improving diagnosis and treatment options for people with hard-to-diagnose CF

Some people may have symptoms of CF but a diagnosis hasn’t been confirmed, as the test results don’t give definite answers. They can live with worsening health for many years, without treatments that could help their symptoms. Many of these people are likely to have rarer CF variants. For some of these people, it is not known whether they may benefit from taking CFTR modulator medicines. 

A Trust-funded Development Award led by Prof Nick Simmonds will investigate whether gut organoids, a test method used in research studies, could be used to in the clinic to provide more certainty for people whose CF is difficult to diagnose. They will also investigate whether the same technology could be used to find out if individuals may benefit from CFTR modulator medicines. Prof Simmonds from the Heart and Lung Institute at Imperial College London will lead a research team including lab and hospital-based researchers in London and Utrecht in The Netherlands. Read more about their ‘ADVANCE-CFTR’ research programme. 

There is potential to design new and innovative medicines to act on the CFTR protein that will make a bigger difference for more people with cystic fibrosis. These improvements can only be made by increasing our detailed understanding of faulty CFTR proteins and exploring novel ways to correct them.

Getting the CF protein into shape

Careful study of the shape, properties and function of the CFTR protein and how these are affected by CF mutations is underway in our Goodchild SRC on CFTR folding and function led by Professor David Sheppard at the University of Bristol. This research may pave the way for more effective CFTR modulators, that work for a larger number of different CFTR mutations.

Read more about Professor Sheppard’s Goodchild SRC on CFTR folding and function

How the CF protein transports bicarbonate

The CFTR protein acts as a gate allowing the movement or transport of two chemicals - chloride and bicarbonate - out of cells. Researchers have conducted many studies to understand how chloride transport is affected in cystic fibrosis, but they know less about how bicarbonate transport defects lead to the symptoms of CF. A greater understanding of bicarbonate transport could lead to improved treatments for CF tailored to individuals. The Trust is funding an SRC programme on bicarbonate transport.

The ‘Restoring the Fizz: Pharmacological repair of bicarbonate transport in cystic fibrosis’ SRC is led by Dr Paola Vergani based at UCL in London. It aims to better understand the flow of bicarbonate in different organs affected by CF. They hope that the results of their lab-based studies will generate ideas on how to treat CF in the future, with medicines more suited to individuals based on the form of CF they have and the severity of different symptoms.

Read more about Restoring the FIZZ SRC on repair of bicarbonate transport

Improving CFTR activity in a novel way

The CFTR protein that is faulty in CF works as a gate.  In people who do not have CF, this gate opens to let chloride and bicarbonate ions flow out of the cell and draws water with them. Without this ion and water movement, the liquid outside cells becomes very thick and sticky, for example on the surface of the lungs and in the GI tract.  The thick and sticky fluid in the lungs is what gives rise to persistent infections that cause much of the lung damage and poor health for people with CF. 

Just like the opening of an ordinary gate, when the CFTR gate is open, chemicals can move in either direction – in or out of the cell.  To keep the lungs healthy, chemicals need to move through the CFTR ‘gate’ from the inside of cells to the outside. One way to keep chemicals moving in the right direction is to increase the levels of potassium inside the cell. The potassium enters the cell through a separate potassium ‘gate’ or channel.

Potassium channel activators as a potential treatment for CF

Treatments currently available for CF are focussed on ensuring that the CFTR gate is working well. In a research study co-funded by the Trust and Action Medical Research, Dr Guy Moss is leading studies in the lab to test whether medicines that act to boost the activity of potassium channels could be effective treatments for CF. 

Dr Moss and UK-based colleagues will investigate whether potassium channel activators can improve the effectiveness of CFTR modulators. They will also investigate whether new combinations of potassium channel activators and other medicines might be an effective way to treat people who are not able to benefit from CFTR modulators.