Primary ciliary dyskinesia – restoring cilia to prevent lung damage

Posted by egg3 at Jan 06, 2015 10:05 AM |
Collaboration between Great Ormond Street and The Institute of Child Health

Dr Robert Hirst is collaborating on an exciting new research project to try to correct mutations that cause PCD in children.

Some of the research will be carried out in the Centre for PCD Diagnosis and Research at the RKCSB in the Department of Infection, Immunity and Inflammation at the University of Leicester.

Background

Primary ciliary dyskinesia (PCD) is an inherited genetic disorder present from birth. It affects cilia, the microscopic hairs which grow out of the cells lining the airways. Each cilium beats over a million times a day moving mucus out of the nose and lungs providing our first line of defence against infection. In the UK, around one in 20,000 children is born with PCD. In the British Asian population, it is much more common with one in every 2,000 children affected. In children with PCD, the cilia cannot beat properly, mucus builds up in the lungs resulting in chronic infection and very severe lung damage, with some children even needing a lung transplant. Sinus and nasal problems are also common and many children have a very significant hearing loss. In forty per cent of children, PCD is caused by a single mutation in a gene that makes a protein needed for the cilia to beat properly. This type of mutation is called a nonsense mutation. There is increasing evidence that certain drugs can overcome nonsense mutations in other diseases and the aim of this study is to see if these drugs are also effective in PCD.

The research project

These researchers have access to a large cohort of patients where the genes responsible for PCD have already been characterised (research also funded by Action Medical Research). They now plan to test two drugs on cells from patients known to have nonsense mutations causing PCD. Both drugs are known as ‘readthrough’ therapies and have been shown to be able to bypass nonsense mutations in other genetic disorders. Gentamycin has been in clinical use as an antibiotic for many years, and ataluren is a newer drug which is currently being studied as a form of gene therapy in cystic fibrosis and Duchenne muscular dystrophy. The aim of this study is to determine if these drugs can overcome nonsense mutations in PCD and make cilia beat normally again. Restoration of normal ciliary beating would essentially cure the underlying disease, markedly reducing subsequent lung damage, sinusitis and hearing loss. There is already good evidence to support the safety of these drugs in humans, so if the results of this research are successful, the team hopes to be able to quickly move forward into a clinical trial in patients with PCD.

Full information about this research is on the Action Medical Research website

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