A genetic disease caused by a single gene mutation

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Cystic Fibrosis (CF) is a genetic disease caused by a single gene mutation and inherited as a recessive allele. A mutation in any part of gene that codes for Cystic Fibrosis Transmembrane Regulatory (CFTR) protein can affect its main function as a chloride pump in epithelial membranes. With faulty CFTR protein, the mucus becomes thick and sticky. As a result, the mucus accumulates inside the lungs, making the bacteria to grow more likely and causing breathing problems as well. This can lead to lung damage and lung infections.(1) Moreover, it also affects other body systems such as digestive system, reproductive system and the sweats glands. However, I choose to focus on the lung problems since the symptoms are very common among the CF patients. Currently, there are no cures for CF, but treatments have been improved greatly in recent years. So, what could be the solutions to reduce the symptoms in CF patients?

Figure 1 : The faulty CFTR protein in CF patients

Source : http://www.childsdoc.org/fall97/cf/cf.asp

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Possible Solutions

After some research, I found that drug treatments are the most effective method in treating CF symptoms. Most people who have CF will take a range of drugs to improve their health and protect them against the symptoms of the disease. Nowadays, there are several kinds of drugs used to treat CF patients. However, the most common are antibiotics and mucolytics.


Antibiotics are used to fight infection-causing bacteria. Infections are common in the lungs of people with cystic fibrosis, so antibiotics are an important part of regular care.

Source : http://www.cff.org/treatments/Therapies/#Alternative_Therapies

Based on the extract above, we can see that antibiotics are effective in reducing the symptoms of lung problems in CF patients. Moreover, antibiotics enhance the mechanisms of lungs and protect them from getting worse. For example, infection from P. aureginosa has a negative impact on lung mechanism and makes the pulmonary inflammation becomes more likely. In the early stage of P. aureginosa colonisation, antibiotics can prevent the shift to serious mucoid infection. So, inhaled tobramycin or the mixture of inhaled colistin with oral ciprofloxacin has been used to overcome the problem.

In a trial, patients that are treated with inhaled tobramycin at a dose of 80 mg twice a day have avoided serious infection caused by P. aureginosa. Moreover, there is eradication of the bacteria in 14 out of 15 treated patients.(25) Nowadays, patients with chronic P. aureginosa infection are being treated with both colistin (21 IU) and tobramycin (80 mg twice a day). Hence, the use of antibiotics is necessary for CF patients.

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Table 1 : A wide range of antibiotics taken by CF patients

Source : http://www.uspharmacist.com/content/t/respiratory_disorders/c/10286/

Based on table 1, there is a wide range of antibiotics that being taken by CF patients. For a chronic infection, two or more different antibiotics may need to be taken at a particular time. Hence, antibiotics are important for preventing the infection in CF patients.


Mucolytics cause mucus to be thinner and less sticky by dissolving it in the lungs or intestines. The examples of mucolytics are N-acetylcysteine (NAC) and dornase alfa (Pulmozyme). The following extract explains about their functions as mucoactive agents.

N-acetylcysteine (NAC) and dornase alfa. Both agents are primarily mucolytic in their action, disrupting disulfide bonds in mucus (NAC) or enzymatically breaking down DNA (dornase alfa) in airway secretions.

Source : Markus O. Henke; Felix Ratjen (2007), Mucolytics in cystic fibrosis, Paediatric respiratory reviews, Vol. 8, 24-29.

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NAC affects the arrangement of the mucus polymer. This is done by substitution of free thiol (sulfhydryl) groups for the disulfide bonds which are connecting the mucin proteins. This resulting in both the elasticity and the viscosity of the mucus are lowered. Its activity is more likely with higher pH and is the best within a range of 7.0-9.0. On the other hand, dornase alfa reduces the surface adhesivity and viscosity of CF sputum. This is shown by a drop in the amount of the DNA in the sputum.(27) It is effective and safe even in patients with severe pulmonary disease which can be defined as a forced ventilator capacity (FVC) < 40% of predicted value.(27)

Nearly 10% of the CF mucus can be attributed to DNA and being removed primarily from airway neutrophils. The extreme DNA content of CF mucus causes its abnormally high viscosity. It was proved that the viscosity of airway secretions could be reduced by aerosolized bovine pancreatic deoxyribonuclease-1. As a result, by using recombinant DNA technology, the development of recombinant human deoxyribonuclease-1 (rhDNase) has provided a major therapeutic advance for patients with CF.⁽⁹⁾ Besides, rhDNase is also known as dornase alfa.

The efficacy and safety of nebulised rhDNase have been obtained in Phase I and II trials. Then, a multi-centre known as double-blind placebo-controlled Phase III trial was established to investigate its long-term effectiveness in children and adults. In the trial, 968 CF patients (> 5 years of age and FVC > 40% of predicted) were distributed randomly to three groups which are to 2.5 mg rhDNase daily, 2.5 mg rhDNase twice daily and placebo for 24 weeks. From that, the main findings were a drop of 31% in the relative risk of a pulmonary exacerbation and the improvement of pulmonary function as measured by a 5.8% increase in forced expiratory volume in 1 second (FEV1) in the rhDNase groups.⁽⁹⁾ The results also showed that the twice-daily dosing was slightly more effective compared to once daily dosing. These results are encouraging and nowadays almost 40% of all CF patients in US receive rhDNase.

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Figure 2 : The percentage in CF pipeline by drug class/technology in 2006

Source : http://www.datamonitor.com/store/News/cystic_fibrosis_enzymes_and_antibiotics_dominate_the_pipeline?productid=B4AAA127-0DD8-4A9D-AF4C-93D277911335

Based on figure 2, 54% of the share is associated with the development of both antibiotics and enzymes. On the other hand, only a small part of that involved an anti-inflammatory. Besides, ion channel therapy and mucolytics each contributes for a 20% share of the pipeline. Hence, antibiotics and mucolytics are being considered as the major therapies in drug treatments.

Benefits and Risks

Drug treatments are effective and can reduce many symptoms of the CF. Besides, people do get better after proper drug treatment, thus can have an opportunity to lead peaceful and meaningful lives in communities again. So, this can enhance the quality of life.⁽⁹⁾ For instance, antibiotic therapy in CF can improve patient well-being , reduce the burden of serious infectious destruction of lung tissue and the ability to live on their own, and, ultimately, to prolong survival. However, inhaled antibiotics may have some side effects and common side effects of antibiotics are nausea, mild diarrhea and even skin rashes.⁽⁵⁾ Besides, some people are allergic to certain antibiotics.

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Mucolytics help to improve mucus clearance from the airways. Hence, they have the potential to reduce the symptoms and allow the body to work as effectively as possible. Similarly, the average life expectancy for CF patients can be increased all the time.

Mucolytics work well for only a few people. Some people have allergic reactions from using acetylcysteine (Mucomyst), and a bronchospasm may occur.

Source : http://health.yahoo.com/respiratory-medications/mucolytics-for-cystic-fibrosis/healthwise--hw186292.html

The above extract explains the risks of mucolytics in certain people. In addition, side effects like vomiting, nausea, drowsiness and clammy skin also may happen. Besides, acetylcysteine can irritate the lungs and causes more coughing. Moreover, it is quite expensive and has a bad taste and smell too.⁽⁸⁾ Furthermore, sodium bicarbonate given via aerosol that been used for mucolysis is also related with bronchospasm and local irritation.⁽⁹⁾

Implications of cystic fibrosis

Social issue

There are 3 aspects of the psychosocial effects of CF on the adolescent or young adult which are the effect on relationships, the effect on the family and adherence to treatment.⁽¹²â¾ Patients with CF would be more likely to be depressed and may have low self-esteem. Poor self-esteem could affect relationships, family interactions and also the social support. Furthermore, teenagers or adults who have CF may have problems in communicating with other people due to their negative views of themselves. Hence, good information and support can reduce negative views on them but the treatments continue to cause difficulties especially for young people. Hence, further studies are needed into the psychosocial impact on CF patients as there are increasing numbers of teenagers and adults with the disease.

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Economic issue

Figure 3 : Pie charts illustrating the percentage of costs attributable to various services for CF patients

Source : http://pediatrics.aappublications.org/cgi/content/full/103/6/e72

The annual cost of medical care in 1996 averaged $13 300 and ranged from $6200 among patients with mild disease to $43 000 among patients with severe disease.

Source : http://pediatrics.aappublications.org/cgi/content/full/103/6/e72

From the above extract, it can be concluded that the health care for CF patients is very costly. For example, based on the pie charts, of total costs, 10% were from outpatient antibiotics, 12% were from clinic visits, 18% were from DNase (Pulmozyme) and 47% were from hospitalization. When these costs were used to determine the costs of health care for the whole population of CF patients in the United States, these costs were determined to be $314 million per year. It is concluded that the amount of health care for CF patients varies greatly with severity but it is substantial even among patients with mild disease. So, a lot of money would be used for the entire life as the disease could not be cured.

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Alternatives solutions

There are other alternatives of treatment for CF patients in order to maintain their health such as chest physical therapy and also the latest treatment which is gene therapy.

Chest physical therapy

Chest physical therapy is a treatment for CF and also known as chest clapping.⁽¹â¶â¾ Generally, this therapy involves the pounding of the chest and back over and over again to dislodge the mucus from the lungs so that the mucus could be coughed up. When certain parts of the back and chest are percussed, the waves produced are transported through the chest wall and thus loosening the airway secretions. However, the child should be positioned appropriately so that the airway secretions will then flow into the upper airways. After that, the excessive mucus can then be cleared by coughing and deep breathing methods. These techniques are the components of chest physical therapy.⁽¹â·â¾ However, this therapy has some challenges because needs training and skill. So, this therapy can only be performed by a nurse, a therapist or an experienced family member. Chest physical therapy for CF patients should be done three to four times each day. Children from newborns to adolescents can be treated by chest physical therapy but it still depends on the health situation and also the specific technique.

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Figure 4 : Several techniques in chest physical therapy

Source : http://www.mountnittany.org/assets/images/krames/102363.jpg

Gene therapy

Gene therapy involves the taking of a copy of the healthy gene and an effective way must be developed in order to get it into the target cell, so that the correct protein can be produced. (19) CF could be cured if effective and safe techniques could be found to replace the faulty CFTR gene by using an intact gene in the target tissues. Normally, the process of gene therapy in CF involves the inhaling of a spray that carries healthy DNA to the lungs. The aim is to replace the faulty and defective CFTR gene in the lungs. This can cure CF or slow down the development of the disease.(20) During such a treatment, vectors will be used to deliver a healthy copy of the faulty gene to the lungs. These vectors normally are derived from viruses. Once the healthy CFTR gene gets into the cell, the biochemical machinery of the cell must recognize it, so that it will be used as a template for the production of normal CFTR protein.(19) However, the effective CFTR protein can only lasted for a few days. This is due to problem that epithelial cells are constantly shed and being replaced by new cells that made by the body. These new cells contain the faulty gene so the new gene is lost. Hence, further studies are ongoing to make it more effective.

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Figure 5 : The use of vector in gene therapy

Source : https://mrcovingtonsciencepage.wikispaces.com/file/view/340px-Gene_therapy.jpg/33783627/340px-Gene_therapy.jpg


The objective of the website http://www.nlm.nih.gov/medlineplus/cysticfibrosis.html is to provide information, support and education related to CF. Besides, this website contains a lot of reviews of the disease. From my opinion, this website is very trustable because the information mainly comes from the National Heart, Lung, and Blood Institute which is a reliable institute. Therefore, the information on the site should be factual. Furthermore, the website is constantly updated. Hence, the information provided should be valid at the time it is published.

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The "Medical Genetics" by Ian D. Young provides brief information about CF and also the gene therapy. The information should be factual since it is written by the well-known specialist in genetic disorders. Besides, there are some information found on the book has similar content to the website http://respiratory-lung.health-cares.net/cystic-fibrosis-gene-therapy.php. Thus, the information provided should be reliable as being supported by the other source. However, the book does not specialise to CF only. Hence, only brief and little information could be found in the book.

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