Primary ciliary dyskinesia (PCD) is a rare genetic condition that affects the function of tiny, hairlike structures (cilia) that line the airways. Children with PCD have a persistent cough and face a lifetime of recurrent chest infections, leading to permanent lung damage. Many will also experience hearing loss in childhood. Professor Chris O’Callaghan of UCL Great Ormond Street Institute of Child Health is hoping to identify drugs that can bypass certain gene faults that occur in around one in four children with PCD. His laboratory research ultimately aims to uncover an effective new treatment that can address the root cause of children’s symptoms, restoring ciliary function and improving their quality of life.
How are children’s lives affected now?
Millions of microscopic hairs called cilia line the surface of our nose and airways and are constantly beating to clear away mucus and debris, helping to prevent infection and lung damage. But in children with PCD, the cilia don’t work properly – leading to a build-up of mucus in their lungs, nose, sinuses and ears.
“Babies and children with PCD will have a persistent wet-sounding cough and recurrent chest infections, which can lead to permanent lung damage,” says Professor O’Callaghan. “They will also experience chronic nasal congestion – and many will also have hearing problems.”
Sadly, there’s no cure for PCD – although exercise and daily physiotherapy sessions can help relieve symptoms by removing some of the mucus from a child’s lungs. Long-term chest infections may require treatment with multiple courses of antibiotics and other therapies, with children sometimes needing to stay in hospital.
“PCD is a lifelong illness that can seriously affect a child’s quality of life,” says Professor O’Callaghan. “New treatments are urgently needed to help improve the lives of children and their families.”
How could this research help?
“Our ultimate goal is to develop a new drug treatment that can help alleviate symptoms in children with certain gene faults that occur in around one in four children with PCD,” says Professor O’Callaghan.
In previous research funded by Action, the researchers developed a new system that allows huge numbers of cells to be grown from samples from patients with PCD. They have now collected samples from over 70 affected children – and plan to use their expanded new cell models to search for potential drug treatments.
“We will test the effects of several drugs, alone and in combination, on cells grown from PCD patients with a certain type of gene fault that stops cilia from working normally,” says Professor O’Callaghan.
The team will use microscopic techniques to find out if any of these drug treatments can ‘override’ the gene faults and restore ciliary structure and function.
|Project Leader||Professor Chris O’Callaghan, BMed Sci BMBS FRCP FRCPCH DM PhD FRSB PFHEA|
|Location||Infection, Immunity and Inflammation Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London|
Professor Hannah Mitchison, BSc PhD
Professor Stephen L Hart, BSc PhD
Dr Rob E Hynds, BSc PhD
Dr Claire Smith, BSc PhD
Dr Rob Hirst, BSc PhD
Genetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London
Regenerative Medicine Research and Teaching Department, Great Ormond Street Institute of Child Health, University College London
Respiratory Sciences, University of Leicester
|Grant Code (GN number)||GN2997|