REVIEW DIAGNOSIS OF CYSTIC FIBROSIS AND THE POTENTIAL OF PERSONALISED MEDICINE AS A CURE OR TREATMENT
SOPHIE HUGHES
Abstract
Diagnostic methods for Cystic Fibrosis (CF) relate directly to the symptoms a patient may be displaying; the connection between symptoms and diagnostics allows for the development in tools and thereby more efficient, reliable and specific diagnostics from the use of clinical or genetic tests. Personalised medicine potential for CF treatment is bright, gene therapy advancements allows for a more targeted treatment focussed on the defected Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene.
1.0 INTRODUCTION
Cystic Fibrosis (CF) is an autosomal recessive disorder. ‘Mutations in the CFTR gene cause cystic fibrosis. The CFTR gene provides instructions for making a channel that transports negatively charged particles called chloride ions into and out of cells.’ (Genetics Home Reference, 2017).
Although the world of medicine has mainly used clinical features such as coughing and sweat to diagnose and treat CF, advancements are being made in gene therapy which target the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene and can eradicate the disease.
2.0 CLINICAL FEATURES LEADING TO DIAGNOSIS OF CYSTIC FIBROSIS
A patient presenting respiratory, reproductive and digestive symptoms would be indicative of CF.
‘People who have CF have thick, sticky mucus that builds up in their airways’ (NHLBI, 2017). A consequence of mucus blocking the airways is that this allows for bacteria to cause infections and thereby frequent coughing and sputum production. ‘lung infections caused by bacteria called mucoid Pseudomonas are much more common in people who have CF than in those who don’t.’ (NHLBI, 2017). Discovery of mucoid Pseudomonas being present in a patient enables the diagnosis of CF.
Digestive symptoms such as ongoing diarrhoea, stomach pain or severe constipation may present in a patient with CF; ‘mucus can block tubes, or ducts in your pancreas’ (NHLBI, 2017). Vital enzymes are incapable of reaching the intestines when these blockages occur, this leads to fats and proteins not being absorbed and therefore the presenting digestive symptoms of CF.
‘Men who have CF are infertile because they're born without a vas deferens’ (NHLBI, 2017). Diagnosis could be made if a male patient was having trouble with fertility. ‘Women who have CF may have a hard time getting pregnant because of mucus blocking the cervix’ (NHLBI, 2017). Fertility can also be used in the case of female patients for diagnosing CF.
2.1 CARRIER AND NEWBORN DIAGNOSIS
As CF is an autosomal recessive disorder carriers could be identified when the CFTR gene was discovered as the cause. Although it is not always guaranteed that the carrier will produce offspring affected by CF, being able to identify a carrier can emotionally benefit families in preparation.
‘the carriers of CF mutations have no biochemical or physiologic alterations by which they could readily be identified’ (Grody and Desnick, 2001). The identification of the CFTR gene allowed for easier diagnosis of CF as the mutation of this gene is unique to the disease; presenting biochemical and physiological symptoms are not always unique to CF and rather could be seen in various diseases.
‘CF newborn screening (NBS) was first in Colorado (1982) and then Wisconsin (1985). Early data from these two centers demonstrated improved nutritional and cognitive outcomes in infants diagnosed by CF NBS compared to those diagnosed on clinical grounds’ (Voter and Ren, 2008).
2.2 SWEAT TESTING
‘The loss of CFTR function in CF patients leads to elevated levels of sodium and chloride in the sweat because of poor reabsorption of these electrolytes in the sweat duct’ (Voter and Ren, 2008). By analysing electrolyte concentrations in patients sweat a clinician can diagnose CF.
Implications for a patient losing sodium and chloride in sweat are vast. Dehydration and fatigue would be a result from the loss of salt in body. Blood pressure may also be altered negatively. These symptoms may be brought to the attention of a clinician leading to diagnosis of CF.
2.3 OPPORTUNITY FOR PERSONALISED MEDICINE
Use of personalised medicine is advantageous to modern medicine as it allows for a more specific therapy which takes into consideration individual cases rather than just a general view. ‘Personalized medicine (PM) has the potential to tailor therapy with the best response and highest safety margin to ensure better patient care. By enabling each patient to receive earlier diagnoses, risk assessments, and optimal treatments’ (Vogenberg, F.R., et al., 2010).
The defected gene CFTR responsible for CF is the first step towards personalised medicine. Rather than just treating the respiratory and digestive symptoms medicine is rather moving toward gene targeted methods where the CFTR can be treated and thereby eradicated.
‘Diagnostic testing involves identifying current disease states. This includes prenatal and newborn screening’the most common forms of genetic testing. Carrier testing determines whether an individual carries a certain genetic trait.’ (Fulda, 2006)
The potential for better treatment of CF in the future due to personalised medicine is huge, as gene therapy continues to advance it could one day provide a cure for CF. ‘To understand personalized treatments designed to correct the basic CFTR defect, a working understanding of the various mutational classes and the mechanisms of CFTR dysfunction are required.’ (Quon and Wilcox, 2015).
3.0 SUMMARY
CF is diagnosed through evaluation of clinical implications of the disease such as digestive problems, respiratory problems or electrolyte problems. Molecular or genetic tests may be used; genetic tests are able to identify carriers.
Gene therapy advancements are now allowing for personalised medicine for cystic fibrosis, meaning treatments are becoming more tailored to individuals and looks at the CFTR gene which causes CF itself.
References
Fulda, K. (2006). Ethical issues in predictive genetic testing: a public health perspective. Journal of Medical Ethics, 32(3), pp.143-147.
Genetics Home Reference. (2017). Cystic Fibrosis. [online] Available at: https://ghr.nlm.nih.gov/condition/cystic-fibrosis#genes [Accessed 12 Dec. 2017].
Grody, W and Desnick, R. (2001). Cystic fibrosis population carrier screening: Here at last’Are we ready?. Genetics in Medicine. 3 (3), 87-90.
NHLBI. (2017). What Are the Signs and Symptoms of Cystic Fibrosis? – NHLBI, NIH. [online] Available at: https://www.nhlbi.nih.gov/health/health-topics/topics/cf/signs [Accessed 12 Dec. 2017].
Quon, B. S., & Wilcox, P. G. (2015). A new era of personalized medicine for cystic fibrosis ‘ at last! Canadian Respiratory Journal’: Journal of the Canadian Thoracic Society, 22(5), 257’260.
Vogenberg, F. R., Isaacson Barash, C., & Pursel, M. (2010). Personalized Medicine: Part 1: Evolution and Development into Theranostics. Pharmacy and Therapeutics, 35(10), 560’576.
Voter, K. and Ren, C. (2008). Diagnosis of Cystic Fibrosis. Clinical Reviews in Allergy & Immunology, 35(3), pp.100-106.