Cystic fibrosis: developing a new type of gene therapy

Around 10,400 people in the UK, including more than 4,000 children, are living with cystic fibrosis.¹ It is an inherited condition, with a range of symptoms caused by a build-up of thick sticky mucus and affecting many organs. Sadly, two people with cystic fibrosis will lose their lives every week, with lung damage due to regular chest infections a big factor.² Professor Stephen Hart at UCL Great Ormond Street Institute of Child Health is aiming to develop a new type of gene therapy that can restore normal function in affected lung cells. He hopes that this work will one day benefit children and adults with cystic fibrosis – helping them to live longer, healthier lives.

Action Medical Research and the Cystic Fibrosis Trust are together funding this study

How are children’s lives affected now?

Cystic fibrosis is the UK’s most common life-threatening inherited disease.  It is caused by a faulty gene, which leads to a disruption to the normal movement of salt and water in and out of cells – and a subsequent build-up of thick, sticky mucus in a child’s lungs and other organs.

Children with the condition experience a range of challenging symptoms that heavily impact on their quality of life. Their lungs are particularly affected, and over time the mucus can block and damage their airways, leading to repeated infections and making it hard to breathe.

“Symptoms usually start in early childhood and get slowly worse, with their lungs becoming increasingly damaged – and this can be fatal if it leads to a serious infection or they stop working properly,” says Professor Hart.

Although there is no cure, treatments are available that can help to reduce problems and make the condition easier to live with. But sadly, a child born with cystic fibrosis will have a shortened life expectancy.

How could this research help?

“Our goal is to develop a new gene therapy that can restore the normal movement of salt and fluids in lung cells, correcting the mucus problem in children with cystic fibrosis,” says Professor Hart.

The team will first perform test-tube experiments to identify the most stable, efficient version of the cystic fibrosis gene - in a form of the molecule called mRNA.

“We will then wrap the cystic fibrosis mRNAs in a mixture of protein and fat called a nanoparticle, which we hope will protect and carry it through the mucus and into the lung cells,” explains Professor Hart.

The researchers will then perform a series of laboratory experiments to assess the potential of the nanoparticles at correcting the problems caused by the faulty gene in cells and living systems.

“We hope that our laboratory work will lay the foundations for a new inhaled gene therapy that can one day dramatically improve the lives of children born with cystic fibrosis,” says Professor Hart.

References

1.Cystic Fibrosis Trust. UK Cystic Fibrosis Registry. 2017 Annual Data Report. Published August 2018. https://www.cysticfibrosis.org.uk/the-work-we-do/uk-cf-registry/reporting-and-resources [Website accessed 25 September 2018]

2.British Lung Foundation. Cystic Fibrosis statistics: https://statistics.blf.org.uk/cystic-fibrosis [Website accessed 25 September 2018]