Potential New Therapy for CF
Potential New Therapy for CF Patients-aimed at reducing mucus production.Professor N.G. McElvaney and David Farrell, Research Coordinator, Respiratory Research Department, Beaumont Hospital
Cystic Fibrosis (CF) is an autosomal recessive inherited disorder characterised by mutations in the gene encoding the CF transmembrane conductance membrane regulator protein-CFTR. The clinical characteristics include bacterial colonisation of the lung, production of thick mucus and recurrent infection. Mucus overproduction is often observed as a major symptom in CF and is most likely the major cause of airway obstruction in the condition. Various attempts have been made over the years to improve mucus clearance. Close attention to physiotherapy with particular emphasis on breathing exercises, mucus clearance techniques and the use of aids such as pep masks to improve mucociliary clearance have been helpful. The arrival of a new medication a number of years ago - DNase (Pulmozyme®) - was also very helpful. This medication works by breaking up high molecular weight DNA in CF sputum therefore making it less viscous, easier to cough up thus improving lung function. However, this effect is not always evident in every individual with CF.
More recently attention has turned to ways in which the secretion of mucins, which make up much of the mucus in CF, can be decreased. This work has centred on decreasing the production of a group of particularly sticky mucins including MUC2 and MUC 5AC. These are thought to play a major role in producing thick mucus found in CF that is especially difficult to cough up. Research performed recently in the United States identified a new protein called HCLCA1, which in addition to other activities, regulates the production of some of these ‘sticky’ mucins. Furthermore, subsequent research showed that that this protein was involved in overproduction of such mucins in chronic lung diseases such as chronic bronchitis and emphysema. The company involved in this research has developed an investigational drug which can inhibit the HCLCA1 protein in laboratory experiments, and it is hoped that this will decrease the amount of ‘sticky’ mucins secreted and in doing so make mucus thinner and easier to cough up.
This investigational drug was used in a Clinical Trial in Ireland in 2003 involving 55 patients in various Hospitals. This trial was a randomised, double blind, placebo controlled study, which meant that some patients received the active medication and others received a dummy medication (placebo). This is quite common in clinical trials as it enables Researchers to compare how people do on the drug compared to those who do not receive the drug, i.e., taking the placebo. The trial drug came in tablet form and the dosage was two tablets, which were taken three times daily. Each patient took the drug or placebo for four weeks. The study demonstrated a mild improvement in lung function in those on the active drug compared to those on the placebo. The drug was well tolerated by patients on the study.
A new Clinical Trial of this investigational drug is now being conducted in a number of different hospitals throughout Ireland (details listed below). The study aims to evaluate the safety and efficacy of the drug over the course of the year in people with CF. The format of the trial is similar to the previous trial-randomised, double blind, placebo controlled trial with the same dosaging of drug being used as in the previous trial. Each participant will be in the study for about a year from the time they commence. The study involves 10 visits over the course of the year. These would on average take about 45 minutes each and are on average every 6 weeks. The study involves pulmonary function tests, occasional blood tests, measurement of vital signs such as blood pressure, temperature, etc., and filling out some questionnaires. There are no changes to existing medications whilst on the trial. The trial has been approved by the Irish Medicines Board and National Ethics Committee and is open to CF patients over the age of 12 who qualify.
If you wish to get further information on this trial, please contact:
David Farrell, Research Co-Coordinator at Beaumont Hospital. Tel. 01-8093864.
Active Participating Hospitals:
AMNCH, Tallaght
Beaumont Hospital, Dublin
Cork University Hospital, Cork
Mid-Western Regional Hospital, Limerick
OLHSC Crumlin, Dublin
Our Lady of Lourdes Hospital, Drogheda
Temple Street Children’s Hospital, Dublin
St.Vincent’s University Hospital Dublin
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