Cystic Fibrosis (CF), we’ve all heard of it and it’s likely that we know someone either directly or indirectly, that suffers from the condition. Affecting over 70,000 people worldwide, CF is an autosomal recessive genetic condition, with sufferers being homozygous (the faulty gene is present on both chromosomes) for the mutant cystic fibrosis transmembrane conductance regulator (CFTR) gene.
CF is often characterized by a build-up of sticky mucus within the respiratory epithelium (a layer of tissue lining the airways serving to moisten and protect them) caused by a decrease in cilia function. In the epithelial cells of the airways the cilia exist in a layer called the airway surface liquid (ASL), which lies between a mucus layer and the apical surface of the cell. The function of the cilia is to waft mucus out of the lungs.
CF arises after the mutant CFTR protein fails to inhibit the sodium channel ‘ENaC’ which allows Sodium ions to flow from the ASL into the respiratory epithelium. Ultimately this means that sodium ions are allowed to flow freely from the airway surface liquid into the respiratory epithelium from the ASL via the ENaC channel, with water following suit. This causes a dehydration of the ASL causing the cilia to come into contact with the mucus layer. Cilia cannot move effectively in this environment and thus cannot clear mucus; a build-up of mucus within the respiratory epithelium soon follows.
All this excess mucus causes great discomfort for the sufferer, frequent infections are common as the mucus provides an ideal bacterial breeding ground, physiotherapy is sometimes required to shift the mucus and a daily assortment of pills and injections are required. Current therapy is able to dislodge the mucus from the lungs and several courses of antibiotics are able to stave off infection for the most part. However, the patient’s lung function steadily gets worse and the average life expectancy for a sufferer currently is 41. This does not mean to say that significant progress hasn’t been made in the last few years with regards to treatment; nine years ago the average life expectancy was 28 so substantial advances have been made. However, with bacteria becoming increasingly resistant to antibiotics, a treatment that targets the source of the problem is urgently needed.
A potential treatment may have been found within the latest research that comes in the form of gene therapy. This treatment primarily centres around inserting wild type (healthy) copies of the CFTR gene into the patient’s cells with the aim of producing functional CFTR proteins. This has the potential to alleviate the patient’s symptoms by limiting, via counteraction, the phenomena explained previously.
Scientists have been carrying out trials to test this treatment around the world and have managed to obtain some positive results. They used liposomes (spherical molecules constructed from phospholipid bilayers that are compatible with the membranes of cells in the body) to bypass the defences of the lung and insert healthy copies of the CFTR genes into the patients. A vaporiser was used as a delivery system, making the treatment akin to how salbutamol is administered to asthma sufferers.
Results from the trials indicated a 3% improvement in lung function compared to a 3% decline in participants who received a saline control. Kieran Kelly, a participant in the trial who was interviewed by the BBC shortly after stated that "I did feel a lot healthier. It might have been psychological, but I did feel better in myself.”
As it stands, the treatment has proven no more effective than some of the other drugs currently available to CF sufferers. However, it does provide scientists with a rich new vein of research potential. Scientists are calling for more small-scale clinical trials so as to better determine whether a larger dose would be more effective. Furthermore, researchers also plan to use viral vectors rather than liposomes to deliver healthy genes into patients more efficiently.
Currently, phase I and phase II trials for the liposome based treatment have been completed and the treatment is soon to progress to larger phase III trials, where the treatment will be tested on several hundred people. Ultimately, if the treatment does prove to be successful and passes all clinical trials then it could provide a new lifeline for CF sufferers around the world. A treatment like this could significantly improve a CF sufferer’s quality of life. It should limit the need for large amounts of drugs and physiotherapy by targeting the problem at its source. Currently no such treatment exists on a large scale, and the CF sufferer is still subject to an arduous daily routine to maintain lung function.
So a diagnosis of CF is still a life changing event, however with gene therapy taking treatment in exciting new directions, within the next few years we could see significant improvements in a patient’s quality of life, certainly a breath of fresh air for all those whose suffer.