Gene Therapy for Cystic Fibrosis Challenges and Strategies Assessment Answer

Introduction

Gene therapy is a method that is associated with the field of medicine and treats or, more accurately, prevents disease by addressing the fundamental issue that is linked to genes. The technique of gene therapy, which is also often known as gene transfer or gene addiction, was developed to introduce a new gene into cells to assist in the fight against the disease. Instead of using drugs or undergoing surgery, gene therapy allows a doctor to treat a patient's condition by effecting changes in the patient's genetic composition. This eliminates the need for either of those treatment modalities (National Library of Medicine, 2022). Gene therapy helps treat both acquired disorders like leukaemia and genetic disease like sickle cell disease (National Human Genome Research Institute, 2023).In gene therapy, an unhealthy gene is either supplemented with a healthy gene or replaced with a healthy gene to strengthen the body's resistance to disease. Gene therapy is also employed when foreign substances enter the body and the immune system is unable to distinguish them; in this case, the use of gene therapy can assist the immune system in recognising the foreign substances. Another use of gene therapy is to fix the mutated gene that could cause disease. Replacement of the defective genes also helps in treating certain diseases. For example, the p53 gene normally works to stop the growth of tumours, and mutations in the p53 gene have been linked to numerous types of cancer; but, if the damaged gene-gene can be replaced, this may permit cancerous cells to multiply (Mayo Clinic, 2017). A new piece of genetic material is introduced into the cell with the assistance of the vector. Before being administered to humans, the viral vectors in question are put through a battery of stringent safety evaluations (American Society of Gene and Cell Therapy, 2017). Gene therapy in several forms has made clinical benefits in patients with haemophilia, blindness, neuromuscular disease, cancer and immunodeficiency (Dunbar et al., 2018). The most recent development in the field of gene therapy has led to the creation of a brand-new method known as genome editing. This method takes a different approach to correcting the genetic disparities between individuals (National Library of Medicine, 2022). 

Cystic fibrosis (CF) is an inherited disease which causes damage that is severe to the digestive system, lungs and other organs.CF affects the respiratory, reproductive and digestive systems. CF also affects the cells that produce digestive juices, mucus and sweat. The people who are suffering from CF have a defective gene that causes secretions of the fluid to become thick and sticky which is slippery in normal people. The secretions clog up the ducts and tubes, especially in the pancreas and lungs (Mayo Clinic, 2021). The mutations result in the creation of a faulty protein that upsets the equilibrium of salt and water in the cells of the body (National Library of Medicine, 2021). The people who experience CF have a worsening loss in the function of the lungs as time passes which leads to the symptoms. The symptoms of CF are divided into two parts. The first part is respiratory symptoms which include shortness of breath, chronic cough and frequent sinus infections. The second is digestive symptoms which include severe constipation, foul-smelling movements of the bowel and inability to gain weight (American Lung Association, 2022). The diagnosis of CF frequently involves a mix of laboratory tests and clinical assessments. To determine whether a newborn has CF, many states now mandate a blood test that checks for high amounts of an agent known as immunoreactive trypsinogen (IRT). Additional tests will be performed to look for CF mutations if the IRT levels are high. A little amount of sweat from the skin is collected for this conclusive test for CF, which involves calculating the salt content of the sweat. High quantities of salt are present in the perspiration of CF patients (Naehrig et al., 2017). To check for CFTR gene mutations, a sample of blood or saliva can be analysed. People with CF symptoms or those with a family history of the condition may undergo this. Doctors may review a patient's symptoms and medical background, as well as conduct physical examinations and other testing to determine the patient's overall health, digestive system, and lung function. Note that CF can be challenging to diagnose, particularly in its early stages. Some people may not exhibit symptoms until much later in life, while others might have subtle or unusual signs that are challenging to spot (De Boeck et al., 2017).

CF is a complicated hereditary condition, and it has been extremely difficult to develop a treatment for it. Many obstacles must be overcome before cystic fibrosis can be cured. To begin, single gene mutations are responsible for cystic fibrosis. The disease is brought on by mutations in the CFTR gene, which is responsible for the production of a protein that contributes to the regulation of the movement of salt and water into and out of cells. On the other hand, the CFTR gene is susceptible to a wide variety of mutations, and each of these changes can have a distinctive influence on the way the protein works in the body. Because of this, it is challenging to devise a treatment strategy that can be applied to everyone (Lukasiak & Zajac, 2021). The second reason is that it can affect a variety of organs, including the lungs, the pancreas, the liver, and other organs; as a result, any treatment would need to focus on several different processes and systems.

The third issue is that cystic fibrosis has the potential to cause irreparable damage to the lungs and other organs over time. This indicates that even if a cure is produced, it may not be able to reverse the harm that has already been done to the body even if it is successful in curing the disease. A large amount of research and development is required to discover novel treatments and cures for CF (Singireddy et al., 2019). This can be difficult to accomplish due to the complexity of the condition, the limited number of patients available for clinical trials, and the high expense of discovering new medicines. In persons with CF, the bacteria that infect the lungs can, over time, develop resistance to antibiotics, making it more difficult to keep infections under control. This can result in lung infections that are both more severe and more common, both of which can cause further damage to the lungs. Although there is a wide variety of medications available to treat CF, not all patients find that these treatments are effective, and there is still no known cure for the disease. This indicates that some people may not respond well to treatment, and other individuals may endure major negative effects from the medications they take (Jaques et al., 2020). Living with CF may be emotionally and mentally taxing, and a significant number of people who have the disease are likely to struggle with anxiety, depression, and other mental health concerns. The ability of a person to adequately manage their sickness may be hindered as a result of these obstacles.

Gene therapy is a viable method to treat CF. The experimental method of treating CF known as gene therapy includes sending a working copy of the gene for the CFTR to the cells that are afflicted with the disease. The mutations lead to the creation of a CFTR protein that is either non-functional or missing. The purpose of gene therapy for cystic fibrosis is to restore the normal transport of salt and water across cell membranes by introducing a functional CFTR gene into the cells that are afflicted by the disease. This would then result in the production of a functional CFTR protein. There are several different methods for treating CF with gene therapy, including both non-viral and viral vectors (Cystic Fibrosis Foundation, n.d.). In the treatment of cystic fibrosis with gene therapy, viral vectors such as adenoviruses, adeno-associated viruses, and lentiviruses are frequently utilised. These viruses are altered to carry a working copy of the CFTR gene, which is subsequently transferred to the cells that are afflicted. However, there are concerns over the safety of viral vectors as well as the immunological response to them, which can limit their usage in clinical applications (Lundstrom, 2018). Gene therapy for cystic fibrosis is also being developed with the use of non-viral vectors such as liposomes, nanoparticles, and DNA complexes. These vectors are often less immunogenic than viral vectors and have the capability of being customised to specific cell types (Zu & Gao, 2018). However, the effectiveness of non-viral vectors in delivering the CFTR gene to afflicted cells is typically lower than that of viral vectors. There has been encouraging progress made in gene therapy clinical trials for CF. However, gene therapy for CF still faces a great number of obstacles, the most important of which is the requirement for the effective transport of the appropriate gene to the appropriate cells in the lungs, as well as the possibility of immune reactions to the gene therapy vectors (Cooney et al., 2018).

References

American Society of Gene and Cell Therapy. (2017). Gene therapy basics. https://patienteducation.asgct.org/gene-therapy-101/gene-therapy-basics

Cooney, A. L., McCray, P. B., Jr, & Sinn, P. L. (2018). Cystic Fibrosis Gene Therapy: Looking Back, Looking Forward. Genes, 9(11), 538. https://doi.org/10.3390/genes9110538

Cystic fibrosis foundation. (n.d.). Gene Therapy for Cystic Fibrosis. https://www.cff.org/research-clinical-trials/gene-therapy-cystic-fibrosis

De Boeck, K., Vermeulen, F., & Dupont, L. (2017). The diagnosis of cystic fibrosis. La Presse Médicale , 46 (6), e97-e108. https://doi.org/10.1016/j.lpm.2017.04.010

Dunbar, C. E., High, K. A., Joung, J. K., Kohn, D. B., Ozawa, K., & Sadelain, M. (2018). Gene therapy comes of age. Science , 359 (6372), eaan4672. 10.1126/science.aan4672

Jaques, R., Shakeel, A., & Hoyle, C. (2020). Novel therapeutic approaches for the management of cystic fibrosis. Multidisciplinary respiratory medicine , 15 (1). https://doi.org/10.4081%2Fmrm.2020.690

Lukasiak, A., & Zajac, M. (2021). The distribution and role of the CFTR protein in the intracellular compartments. Membranes , 11 (11), 804. https://doi.org/10.3390%2Fmembranes11110804

Lundstrom K. (2018). Viral Vectors in Gene Therapy. Diseases (Basel, Switzerland), 6(2), 42. https://doi.org/10.3390/diseases6020042

Mayo Clinic. (2017). Gene therapy.https://www.mayoclinic.org/tests-procedures/gene-therapy/about/pac-20384619

Mayo Clinic. (2021). Cystic fibrosis. https://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/symptoms-causes/syc-20353700

Naehrig, S., Chao, C. M., & Naehrlich, L. (2017). Cystic fibrosis: diagnosis and treatment. Deutsches Ärzteblatt International , 114 (33-34), 564. 10.3238/arztebl.2017.0564

National Human Genome Research Institute. (2023). Gene therapy. https://www.genome.gov/genetics-glossary/Gene-Therapy

National Library of Medicine. (2021). Cystic fibrosis. https://medlineplus.gov/genetics/condition/cystic-fibrosis/#:~:text=Mutations%20in%20the%20CFTR%20gene%20disrupt%20the%20function%20of%20the,is%20unusually%20thick%20and%20sticky.

National Library of Medicine. (2022). What is gene therapy?. https://medlineplus.gov/genetics/understanding/therapy/genetherapy/

Singireddy, S. R. S. R., Varagandhi, S., Jagiri, A. G., & Kadarla, R. K. (2019). An Overview on Cystic Fibrosis. Asian Journal of Pharmaceutical Research and Development , 7 (5), 80-91. https://doi.org/10.22270/ajprd.v7i5.535

Zu, H., & Gao, D. (2021). Non-viral Vectors in Gene Therapy: Recent Development, Challenges, and Prospects. The AAPS journal, 23(4), 78. https://doi.org/10.1208/s12248-021-00608-7

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