Ignoring the Nonsense - Personalised Medicine for Genetic Lung Disorders

Lead Researcher:

Dr Noel McElvaney

Award Date:

1 January 2013

Host Institution:

Irish Thoracic Society

Scheme:

Medical Research Charities Group Co-Fund Award

Summary:

Cystic fibrosis (CF) and alpha-1 antitrypsin deficiency (AATD) are the most common genetic lung conditions in Ireland. An estimated 1 in 20 Irish individuals are carriers for CF, with a further 1 in 25 carriers for AATD. This means the prevalence of each condition in Ireland is among the highest in the world. Currently, there are approximately 1,200 cases of CF and 200 cases of AATD diagnosed in the country. However, we know there are up to 2,000 MRCG/HRB Joint Funding Scheme 2013 - Application Form, Page 4 people in Ireland with AATD but the vast majority have been misdiagnosed with COPD or severe asthma, or have not developed symptoms yet. Both CF and AATD are caused by changes in a single gene. These changes are called mutations, and there are several kinds of mutation. For example, up to 10% of all cases of CF are caused by "nonsense" mutations and these mutations can also cause AATD. A nonsense mutation acts like a full stop in the middle of a sentence, and similar to language, this leads to a loss of meaning and prevents the production of normal working proteins. If drugs can be developed to remove these damaging full stops, we can prevent lung disease developing and effectively cure these individuals.
We have obtained a variety of drugs designed to remove the harmful full stop and we will test them on cells taken directly from CF and AATD individuals with nonsense mutations. Using blood cells taken from affected individuals who attend our centre, we hope to cure the precise genetic defect, rather than continuing to treat the symptoms associated with each lung condition.