Cystic Fibrosis, a Problem to Get Off Our Chest

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This week my blog is about Cystic Fibrosis as it is a condition which can cause devastation in families and is a topic of continuous research to improve the quality of life and life expectancy of suffers.

Cystic Fibrosis (CF) is a genetic multi-organ disorder which is usually characterised by mucus clogging up the lungs causing a persistent cough and recurrent chest infections. These chest infections occur throughout a patient’s life and cause lung complications meaning a transplant is often needed. The current life expectancy for CF suffers being born now is 40 years old, but this is continuously increasing with on-going research and new treatments.

What Causes the Condition?

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is a channel that sits in the epithelial lining of cells found in tissues throughout the body. The main function of this channel is to allow chloride (Cl) ions out of the cell to control the movement of water in the bodies’ cavities such as the lungs. Release of the correct amount of water released from these cells allows mucus to flow across the surface, removing bacteria and other potentially harmful particles from the airways.

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The gene that encodes this protein is mutated in patients with CF, and there are  many different possible changes to the gene cause different severities of the condition. The most common mutation is the deltaF508, which is just a fancy way of writing that an amino acid at position 508 is deleted. This causes a change in the protein which means it does not reach the membrane of these cells to release chloride ions.

If chloride is not moved across the membrane of the epithelial cells then the ion gradient necessary for water movement by osmosis is not created. Mucus then becomes thick and sticky and doesn’t flow, this is known as mucostasis. Build up mucus not only stops bacteria being removed, but also gives them a cosy place to grow and cause the classic CF infections.

Other mutations in the CFTR gene allows the channel to reach the membrane without being broken down, but can reduce activity. These types of mutations lead to less severe forms of the disease.

How do Patients get CF?

CF is a genetic condition, as the altered gene is inherited from the parents and passed onto the child. It is an autosomal recessive disorder, meaning it is passed on through a mutation on a non-sex chromosome and if both parents are heterozygous carriers of the gene defect, then the child will only have a 25% chance of developing the condition but a 50% of also being a carrier.

What’s being done to help?

New research is aiming to reduce the breakdown of the CFTR protein with delta F508 mutations. A recent study has attempted to do this using micro-RNA (miRNA) technology. These small molecules can interfere with gene expression meaning that some proteins are not produced. The link between certain miRNA’s found in the cell and the pathology of CF such as airway inflammation is well established.

Previous attempts to treat CF with these methods have come across the barrier of getting the miRNA’s into the cells. McKeirnan’s group at the Royal College of Surgeons[ii] have used nanoparticles which can bind RNA molecules to their surface and travel across the membrane. This is a promising new technique to lower the levels of proteins causing inflammation and reduce damage to the airways.

New drug delivery mechanisms and compounds to treat the different effects of Cystic Fibrosis will hopfully help prevent the need for transplants and give patients a longer, healthier life.

Julia Rose


McKiernan PJ, Cunningham O, Greene CM, & Cryan SA (2013). Targeting miRNA-based medicines to cystic fibrosis airway epithelial cells using nanotechnology. International journal of nanomedicine, 8, 3907-15 PMID: 24143095

photo credit: <a href=”http://www.flickr.com/photos/upton/479164155/”>upton</a&gt; via <a href=”http://photopin.com”>photopin</a&gt; <a href=”http://creativecommons.org/licenses/by-nd/2.0/”>cc</a&gt;

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