Tackling the underlying cause of cystic fibrosis
Cystic fibrosis is a genetic condition caused by having two mutated copies of the CF gene known as ‘CFTR’. The specific mutations present in each copy of the gene is known as a ‘genotype’. The most effective way of treating CF is to restore the function of the protein produced by the mutated gene, known as the CFTR protein.
Research is underway to treat the underlying cause of CF in a number of ways. These include increasing the amount of working CFTR protein in the cell, understanding more about lung clearance and inflammation to improve treatments, developing genetic therapies to produce healthy copies of CFTR, and boosting the function of proteins that work in a similar way to CFTR.
Research into keeping the CF lungs healthier
Thick, sticky mucus in the lungs that is hard to clear makes it more difficult for people with CF to breathe and harder for them to clear infections. However, the detail of how mucus moves in the lungs is poorly understood. Professor Pietro Cicuta at the University of Cambridge is leading a Strategic Research Centre to develop state-of-the-art methods to measure and understand how mucus stretches and moves within the lungs. The results of these research could mean treatments can be tailored for individuals with CF in the future.
In a complementary study, we are co-funding a PhD studentship at UCL through a Venture and Innovation Award to apply computer modelling analysis to understand more about mucus clearance and how to improve it in cystic fibrosis.
Within the guts (also known as the intestines) there are many different types of bacteria that help the body to digest food. The proportion of bacteria within the intestines is altered in CF and this can trigger inflammation in the lungs. To understand more about why this happens and whether changing things in the gut can reduce inflammation we’re funding a Strategic Research Centre led by Professor Daniel Peckham at the University of Leeds.
Read more about research we’re funding on this topic, through our strategic research centre (SRC) and Venture and Innovation Award (VIA) funding schemes:
Understanding and correcting the CFTR protein
Drugs that modulate the function of the CFTR protein are known as CFTR modulators or precision medicines. To date, these have been developed to treat the genetic mutations found in around 90% of people with CF in the UK, for example the medicine Kaftrio.
However, some people with the mutations treatable by CFTR modulators do not respond to the drugs, or they are not able to tolerate them. For the remaining 10% of people there are no treatments that address the underlying cause of CF.
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.
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 ‘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 is 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.
Investigating genetic treatments
The discovery of the CFTR gene over 30 years ago led to interest in the development of genetic therapies for cystic fibrosis. 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. Methods of treating CF on a genetic level include gene therapy, mRNA therapy and different types of gene editing. An important aspect to developing an effective genetic therapy is safely and effectively delivering it to the correct place in the body.
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 genetic editing therapies for cystic fibrosis.
Alternative ion channel therapies as treatments for everyone
Dr Mike Gray and colleagues are conducting research to see if alternative proteins can be either activated or blocked to compensate for the lack of working CFTR protein. In a Trust-funded Strategic Research Centre, they are looking for medicines that act on ‘alternative chloride channels’ and are investigating how these channels might work.
Regenerating damaged lungs
Trust-funded researchers within the CF Innovation Hub based at Cambridge University are investigating how to repair any damage that has already been caused in the lungs of people with CF.
Research we fund
We fund research to tackle some of the most pressing issues in CF today. Find out how your donations are making a difference.
What is CF?
Cystic fibrosis, or CF, affects the lungs, digestive system and other organs. There are around 11,000 people living with it in the UK.
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