Cystic fibrosis cure on horizon after scientists fix genetic mutation

·3 min read
Collapsed organoids (left) swell up after genetic treatment (right), demonstrating that they are now functioning correctly - Eyleen De Poel/UMC Utrecht
Collapsed organoids (left) swell up after genetic treatment (right), demonstrating that they are now functioning correctly - Eyleen De Poel/UMC Utrecht

A cure for cystic fibrosis is on the horizon after scientists corrected the genetic mutation that causes the condition in human cells.

Around one in 2,500 babies are born with the condition, which causes a build up of thick, sticky mucus in the body, blocking the lungs and digestive organs. It is caused by a faulty piece of DNA that fails to produce enough water to dilute the mucus.

Now scientists from the Hubrecht Institute, in the Netherlands, have shown that a healthy piece of DNA can be swapped for the defective code, allowing cells to function normally.

In mini-intestinal organs grown from human stem cells – known as organoids – the team showed that inserting the new DNA into the malfunctioning tissue caused the cells to plump up with extra fluid.

"The treated organoids demonstrated the same response as the healthy organoids – they became swollen," said Dr Maarten Geurts, first author on the study. "That provided us with proof that our technique worked and replaced the mutated DNA.

"We have, for the first time, demonstrated that this technique really works and can be safely applied in human stem cells to correct cystic fibrosis."

Cystic fibrosis is one of the most prevalent genetic diseases worldwide, and means patients must take a range of medications and undergo regular airway clearing treatments and exercises.

Around 10,600 people in the UK suffer from the condition. According to the Cystic Fibrosis Trust, one person in 25 carries the faulty gene, usually without knowing, meaning two million people in Britain have the mutation.

If two carriers have a child, it has a one in four chance of developing the condition, which can bring symptoms including a persistent cough, wheezing, breathing difficulties, repeated chest infections and lower life expectancy.

For the new research, the team used a technique called Prime Editing, which is a variation of the genetic snipping tool Crispr.

The new technique inserts genetic material without inadvertently causing damage elsewhere, so is less likely to bring unexpected problems. It was tested on mini-organs grown from the stem cells of patients with cystic fibrosis and compared to those grown from healthy cell lines.

The mutations that cause cystic fibrosis are found in a channel known as CFTR (cystic fibrosis transmembrane conductance regulator), which is present in the cells of various organs including the lungs.

Due to the mutations, the channel does not function properly, leaving the layer of mucus that covers the cells with too little water and meaning that the mucus becomes sticky.

The technique still needs to be adapted for safe use in humans, but researchers said it was a "big step forward" in applying genetic editing techniques in the clinic to cure devastating inherited disease.

"This will hopefully enable us to cure or even prevent genetic diseases in the future," said Dr Geurts. "New variants of Crispr, such as Prime Editing, can safely correct mutations without causing damage in other regions of the DNA."

The study was published in Life Science Alliance.