How effective is gene therapy in treating cystic fibrosis?

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How effective is gene therapy in treating cystic fibrosis?

The problem

Cystic Fibrosis (CF) is an autosomal recessive genetic disorder that mainly affects the lungs, liver and also affects the intestines. This disorder is caused by a mutation to the CGTR gene, which is located in chromosome 7 (helps control quantity of sodium and chloride ions in cells). Therefore, due to the mutation to the cystic fibrosis transmembrane conductance regulator (CFTR), protein synthesis cannot operate properly1. This protein plays a huge role in regulating components of sweat, digestive fluids and mucus. CFTR monitors the movement of chloride and sodium ions across epithelial membranes such as the alveolar epithelia located in the lungs. Normally, when our CFTR gene is functioning correctly, the cilia in our lungs is used to clear the mucus out of your body. However in CF, due to an overload of thick and sticky mucus, the cilia can no longer, move the mucus along therefore. Severe infections can be caused by this

Cystic fibrosis immensely affects the body’s exocrine glands, causing them to secrete an excess of mucus and other substances. Exocrine are responsible for secreting substances onto body surfaces both internally (such as lungs) and externally (such as the skin). Some very well-known examples of secretions would be sweat, tears, digestive juices and mucus. The main secretion involved in CF is mucus, this affects the lungs (as I explain above) and also the pancreas where the thick mucus blocks the route that would carry important enzymes into the intestine to digest foods. When this happens the body can’t process or absorb nutrients properly, especially fats. Children with CF often struggle to gain any weight, even with a good diet and a good appetite.

CF is most common among people in Central and Northern European ancestry and is rarest in Asia and the Middle East. People can be tested for CF by genetic testing or by a sweat test in your early childhood. In the US, CF is the most common genetic disorder, and in the UK 1 in 2500 babies are born with CF. Currently 9000 people in the UK have CF. CF results in people dying before they reach the age of 40. Between 1996 and 2006, 3708 people in the U.S died from cystic fibrosis.

When the hosts CFTR gene is functioning correctly, there is a correct balance between sodium and chloride ions and also between water. If there is an excess amount of water in the mucus, water is transported out of the mucus into the cell. This happens because of the osmotic pressures caused by the gradients of sodium and chloride ions inside the cell. Also when there is too little water in the mucus the CFTR channel is opened, so chloride ions travel into the mucus, and what follows this is the water travelling from inside of the cell into the mucus making it less sticky. With someone suffering from cystic fibrosis, the CFTR is mutated. The consequence of this would be that Cl ions cannot be transported into the mucus, therefore the sodium transporter opens and travels into the cell. Chloride ions follow to the interstitial side. Water follows through osmotic pressure resulting in thicker mucus.

When two people who carry the CF gene have a child, there is a4:

  • 25% chance that the child will be born with CF (by inheriting the CF gene from both parents)
  • 50% chance the child will not have CF, but will be a carrier (by inheriting the CF gene from one parent but the normal gene from the other)
  • 25% chance the child will have not have CF, and will also not be a carrier (inherits the normal gene from both parents)

Mayo Clinic Staff suggests the following symptoms are experienced by CF patients:

Respiratory signs and symptoms

Digestive signs and symptoms

A persistent cough that produces thick spit (sputum) and mucus

Foul-smelling, greasy stools


Poor weight in gain and growth


Intestinal blockage, particularly in new-borns

A decreased ability to exercise

Severe constipation

Repeated lung infections

Inflamed nasal passages or a stuffy nose

The Solution

Some traditional methods used to treat CF include antibiotics, anti-inflammatories, chest physiotherapy and other remedies such as diet and enzymes. The chart below shows the effectiveness of these treatments in consistently improving the average life expectancy of CF patients, between 1940 and 20066.

Figure 1

Due to new drugs and more therapies, the life expectancy of someone with Cystic Fibrosis hasgrown dramatically in the last few decades as can be seen in the graph above. Between 1950 and 2008, life expectancy has increased almost 19 fold.

However these therapies can only increase life expectancy to 36.8, therefore they are not cures--they are simply treatments. Gene therapy is a possible cure for CF and could bring the life expectancy up to an average persons. Gene therapy would provide a brilliant solution in stopping CF because:

  • It would provide a long term solution to the disorder
  • Germline gene therapy will prevent children from inheriting CF
  • Even a reasonably effective form of gene therapy would have a big impact, increasing life expectancy and improving the quality of life

Somatic gene therapy is an alternative form of gene therapy, which is currently being researched in sight of this treatment being used in the future.

Gene therapy is a type therapy that involves altering the genes inside your body’s cells to stop the disease from spreading or getting worse. Gene therapy replaces a faulty gene or adds new fully functioning gene, in an attempt to cure the disease or improve your body’s defence’s ability to fight against a disease. Gene therapy holds the key to curing a wide range of diseases, such as, cancer, cystic fibrosis, heart disease and AIDS. However more related to the cure to CF, the faulty CFTR gene located in chromosome 7 will be replaced with a fully functioning one5.

Somatic gene therapy in CF8:

  1. This involves the genetic engineering of any cells in the patient’s body apart from the reproductive cells (sex cells, e.g. sperm and egg)
  2. The intention is to make the changes permanent to the individual being treated and the part of the body where the illness is located, therefore the genetic disorder is not passed on to parent’s offspring7.
  3. This process involves the addition of a healthy CFTR gene into the body or cells to replace the mutated CFTR gene
  4. Finally the healthy CFTR gene will start to work and therefore remove chloride and sodium ions to the outside of the cells

Germline gene therapy is a second type of gene therapy, however unlike somatic gene therapy it is currently banned in Australia, Canada, Germany, Israel, Mexico and many other countries9. This is mainly due to the fact that during this process you alter germ cells, therefore changing the genes of potential future persons without their permission. Secondly, the procedure of developing and creating essential materials to be used in germ line gene therapy involve the destruction of embryos, which many people use regard as the equivalent to killing a human being.

Germ line therapy in CF involves the following10:

  1. The corrective gene for an illness such as CF is added to a fertilized egg by injection, this mean genetically modifying the fertilised egg. This will not only effect the individual that develops but also the offspring.
  2. In this case the healthy CFTR gene is inserted and the mutated CFTR gene is removed.
  3. Now a zygote is formed between the sperm and egg. The egg divides twice. A cell is removed for testing to make sure the gene inserted itself correctly. If so the other cells will be implanted into the mother’s uterus.

The National Human Genome Research Institute suggests that gene transfer during the early stages of embryo development can be far more effective than the somatic cell gene therapy which occurs much later in development11. Embryo gene transfer, subsequently gives the chance to change most or all of the organisms and therefore is more effective that the somatic approach. However, this approach poses many uncertainties and risks.

Risks and Problems associated with gene therapy

Gene therapy has some potential risks, this is because there can be some complications when inserting a gene directly into cells. It usually has to be delivered into the cell via a vector, and the most common gene therapy vectors are viruses because they can recognise certain cells and carry genetic material into the cells genes.

The table below shows a summary of the problems and risks associated with gene therapy



The immune system of the organism may recognise the newly introduced viruses as intruders and attack them.

Unwanted immune system reaction. This may cause inflammation and, in severe cases can cause organ failure.

The wrong cells may be targeted for treatment, as viruses can affect more than one type of cell. There’s a possibility that that the viruses may infect additional cells, not just the targeted cells as anticipated.

Healthy cells may be damaged, causing other illnesses or diseases, including cancer.

Furthermore, there can be implications when inserting the gene because it may go into the wrong section and cause a tumour. This has occurred occasionally as I will explain below:

An example of the dangerous nature of gene therapy involves an 18 year old boy named Jesse Gelsinger, who died during a clinical trial for the further research into gene therapy. Jesse died on September 17th 1999. He was with an adenoviral vector carrying a corrected gene to test the safety of the procedure which may be given to the public if approved. He died 4 days later, apparently having suffered a significant immune response triggered by the use of the viral vector used to transport the gene into his cells, leading to multiple organ failure and death of brain tissue13.

Implications of the solution

The most positive social impact of gene therapy on the treatment of CF is that thousands of people would be protected from the disorder and deaths each year. CF affects around 70 000 people worldwide and 55% of these people are younger than 184, the average life expectancy of someone with CF is around 40, but used to be much lower years ago4. Even a moderately effective gene therapy treatment would increase life expectancy and effects thousands of people also reducing the amount of human pain and suffering that CF causes. In addition, CF severely damages children’s schooling and social development through being in and out of the hospital. Sufferers of CF may be treated differently by others due to their disorder so they may be segregated from the normal social activities. Also children will not be attending school as often due to the continuous treatment they require, therefore not interacting with other at school. Later causing emotional distress due to a lack of social interaction.

Alex Stobbs is an example of an individual who experienced these difficulties. Alex has actually featured in two documentaries, the first one called “A boy Called Alex” in 2008 and its sequel “Alex: A Passion for Life” in 200914. He was due to take his finals at Kings College but his health deteriorated rapidly to an unstable condition and he finally forced to leave the University after four lengthy hospital stays. He shows the hardships of being a sufferer of CF especially seen as he is an incredibly gifted musician and hopes to become a conductor even through his struggles. Also Alex is becoming increasingly deaf due to the build-up of mucus in his body15.

Through the years clinical trials have taken place, where we have tested gene therapy on hosts that were willing to have to medication applied to them. In 1999, gene therapy was clinically tested by Zuckerman et al, and he goes on to say there were some safety concerns on the hosts, such as flulike symptoms which were experienced at high doses of gene therapy16. However during most of these trials, there were hardly any safety concerns. In the document, assessing the performance of gene therapy, the outcome of the treatment was also stated. Which shows the effects it had on the host. Obviously no host was treated entirely but there were breakthroughs, in one experiment it was stated that there was some ‘correction of Cl-16, which shows that with more technological advances we can one day make the treatment fully functional.


Over 9000 people in the UK alone suffer from CF, the disease is causes much pain and suffering for the patients. There is no current cure for CF, however gene therapy is a possible future alternative. The process towards making gene therapy completely safe and effective has accelerated in the recent years. Advances in science and in gene therapy technology can bring excitement to the possibility of securing a cure for the future. For now current treatments such as antibiotics must be used to reduce the symptoms that come from CF.


1) What is Cystic Fibrosis? (2014)- Assessed 20th March 2015

2) Disease and conditions – Assessed 20th March 2015

3) Cystic fibrosis – Assessed 20th March

4) Cystic Fibrosis (December 2014) – Assessed 20th March 2015

5) Cystic fibrosis symptoms (2012) - Assessed 21st March 2015

6) Average life expectancy in CF- Assessed 21st March 2015

7) Edexcel AS Biology Student’s book, Ann Fullick


9) Genetics and Public Policy centre (2004) - Assessed 22nd March 2015

10) Germline gene therapy (22nd March 2015) - Assessed 23rd March 2015

11) National Human Genome Research Institute (March 2006) - Assessed 25th March 2015

12) Gene therapy Risks (Jan 2013) - Assessed 25th March 2015

13) Jesse Gelsinger (Oct 2014) - Assessed 26th March 2015

14) Alex Stobbs (July 2014) – Assessed 26th March 2015

15) Brave music prodigy battling terminal disease graduates from Cambridge with 2.1 (June 2012)- Assessed 26th March 2015

16) Clinical trials investigating gene therapy for cystic fibrosis (1993-2004) – Assessed 30th March 2015