Gene Therapy as a cure for Hemophilia

Hemophilia is an inherited disease, particularly a sex-linked recessive disease that mostly takes place in males. This certain disease prevents the patient from forming blood clots effectively. People who are not infected with hemophilia have a normal way of recovering. When the tissues and blood vessels in the body, both inside and outside, are injured and damaged, the blood is exposed and leaks out from the hole of the cut, bruise or internal hemorrhage. When people experience being injured, the platelets that flow in the blood are extremely essential cells that are required to cluster and cover the hole of the injury, enabling the blood to stop flowing out.

However when one has hemophilia, injuries may result to continuous bleeding that can possibly be detrimental to one’s life. The patient may experience one of the two effects. The first being life-imperiling bleeding injuries that have no relation to trauma, and the other being light forms of the disease with non-critical minor injuries, however major traumas may occur that highly risks the patient’s well being, in which these include car accidents and surgery.

In addition, for a patient to have hemophilia means to have a gene mutation in their body. In other words, the gene responsible for blood clothing must have experienced gene mutations of substitution, inversion, deletion or insertion. Blood clotting proteins of Factor VIII and IX are predominantly the factors that were mutated. Estimated to be around 85% of the hemophilia patients are infected with Hemophilia A, in which the body produces too little or no Factor VIII. [1]Mutations of this particular factor are 6% due to large deletions, 43% due to substitution and 51% due to inversions. On the other hand, Hemophilia B is a case where in the patient has a flaw in their Factor IX gene, in which it is caused by deletion or substitution.

Furthermore, both hemophilia A and B are rare diseases. Hemophilia A is estimated to approximately affect 1 in every 10,000 male births. on the other hand, hemophilia B is estimated to approximately affect 1  out of every 25,000 to 30,000 male births. Both diseases are worldwide, in other words, it is preset in all ethnic groups around the world.

Figure 1 below explains the four stages needed to recover from injuries. It compares the blood clotting process of people with no hemophilia and hemophilia patients. The first two actions are the same, bleeding starts and vessels constrict, however the third and fourth step is where the problem exists. With missing blood clotting factors, there is an incomplete platelet plug and as an result an incomplete formation of fibrin clot. Therefore, the bleeding continues and needs medical attention.

Figure 1: How Hemophilia Works
http://www.hemophilia.ca/en/bleeding-disorders/hemophilia-a-and-b/the-clotting-problem-in-hemophilia/

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[1] "Hemophilia." ASGCT. N.p., n.d. Web. 8 Oct. 2014. <http://www.asgct.org/general-public/educational-resources/gene-therapy-and-cell-therapy-for-diseases/hemophilia>.

Medical treatment for the hemophilia disorder is currently in the state of a huge transformation. Researchers and scientists have discovered a new method that is possibly the perfect cure to the many genetic and incurable diseases present in this world. This technique is known as gene therapy, it is the process of inserting and introducing healthy genes into the human body, or other mammalian beings. In other words, genes are utilized as medicine.

Gene Therapy has two different approaches, they are known as the germ-line gene therapy and the somatic cell gene therapy. The germ-line gene therapy targets gametes cells in the gonad organs. It enables healthy functional genes to be injected into either the zygote, an early embryo or an egg or sperm cell as to, hopefully cure the patient, as well as pass it down to their offspring and other future generations. On the other hand, the somatic cell gene therapy targets the other cells of the body. As it does not include sex cells, it has no possibilities of passing down the changes to their children or future generations.

For gene therapy to become a revolutionary breakthrough for mankind, a way for gene delivery to the body must first be invented. Researchers have discovered a particular method that utilizes carriers, which are also known as vectors. These so called vectors are where the genes are kept and contained in and given to the patient’s body. Currently, there are two types of vectors used for gene therapy, in which they are viral vectors and non-viral vectors. Viral vectors are basically virus vectors. The genes of the living virus is genetically engineered as to alter the DNA, in other words the “bad” DNA is deactivated and removed then replaced with functional genes as to contain un-harmful human DNA. Viruses are utilized as they have a replication cycle, where in it charges into a cell and infuses their genetic material into it. These genetic materials are the basic commandments that order the virus to duplicate, thus infecting more and more cells in the body. There are two ways for a virus vector to infect an infected cell. The first method is by exposing the virus to the cell outside the body, or in one word ex vivo. this method is in vitro, as the cells of the patient are extracted and brought into a laboratory, where in it comes in contact with the virus vector. Once the new gene has infected the defective cells, it is returned back to the patient’s body. In contrast, the second method is directly placing the virus vector into the patient’s body, in other words the in vivo method. Figure 2 below demonstrates how the vector works when it meets a cell. The gene will manage on its own to find the infected cell, where it will have to go to the cell’s nucleus then unites with the human DNA. Once done, it needs to be activated, thus producing the needed protein. For the vector to be inserted into the patient‘s body, doctors utilize intravenous infusion or injection into a body cavity or a tumor. Furthermore, the viruses used for gene therapy are mostly retroviruses or adenoviruses, other viruses used include adeno-associated viruses, lentiviruses, pox viruses, alphaviruses and herpes viruses.

Figure 2: Using vectors to transfer new healthy genes to the cells in the body
http://ghr.nlm.nih.gov/handbook/therapy/procedures

Figure 2 above talks about viral vectors. The picture illustrates how vectors and viruses are utilized as a medical treatment with the in vivo method. Specifically, the picture tells us how virus vectors infiltrates the defective cells, and demonstrates how the modified DNA in the vectors are given to the cell. 

Video 1 below shows what is hemophilia and how is gene therapy able to cure this particular disease. It gives a brief explanation of how it works, similar to the paragraph above, before the picture. Furthermore, it also shows Dr. Amit Nathwani and Dr. Andrew Davidoff, researchers on gene therapy for hemophilia, and a patient's views and opinions on this revolutionary treatment. 

Video 1: Hemophilia gene therapy breakthrough (UCL)

http://www.youtube.com/watch?v=11maHFwC35s

On the other hand, non-viral vectors are the opposites. These vectors don’t use viruses and infect a certain cell. According to genetherapynet.com, there are four types of non-viral vectors. They are naked DNA, oligonucleotides, lipoplexes and polyplexes. Scientists insert the functional genes into these vectors and are then injected to the body. Unlike virus vectors, the genes are not infecting the defective cells. Instead, it is injected to the body, where it travels to the location of the defective cells with the mutated genes. Once the vectors manages to find the cell, the functional genes in the vector is either unable to enter the cell or is able to. Between these two vectors of viral and non-viral, viral vectors are more commonly used in clinics and hospitals. Although viral vectors may cause immunogenicity and oncogenicity and has a relatively small space for the genes to be transported, it is claimed and proven to be more effective than non-viral vectors. On the other hand, although non-viral vectors are guaranteed to be more safe for patients, less expensive and more affordable, have a higher chance of reproduction and the space for the gene is unlimited, it has a low possibility of being successful and effective for the patient.

For every treatment to a disease, there will always be benefits and limitations present. Gene therapy, as a medical remedy, is an optimistic technique to society, particularly those with incurable diseases, however there are still some drawbacks to it. One of the beneficial gains of gene therapy to hemophilia is that mutated genes can be repaired, thus the proteins of clotting factors in the blood will increase. As a result, the time for the patient’s injury to clot will decrease. Although, the results might be quite small, it is extremely essential and convenient to the patients. 

Another advantage of gene therapy to hemophilia is that hemophilia patients are able to live a normal life. They are given the chance at a normal life with no problems and complications concerning their body and health. They don’t have to worry about the possible difficulties that might arise within themselves, such as sudden pain and swelling in joint regions, immoderate bleeding from cuts, injuries and any form of medical work (includes surgery and dental work), constant vomiting and severe fatigue. Figure 3 below demonstrates one struggle experienced by a hemophilia patient, in which it is the pain and swelling of a joint, particularly in the knees of the patient. It is unable to heal and recuperate well, thus bleeding does not stop. Therefore, the knee joint becomes larger and larger and swelling occurs. The patient is exposed to suffering when doing daily activities. 

Figure 3: One of the many Hemophilia symptoms
http://www.canstockphoto.com/joint-bleeds-in-hemophilia-11382316.html

As I have said before, every medical treatment will, unfortunately, have some drawbacks and limitations. Most of these limitations present are concerning technology and science. One of the many is a technological problem regarding the use of gene therapy. The main concern of gene therapy is that the viruses may target the wrong cells in the body. These viruses tend to not target the defective cells, and instead fuses with other random cells of the body and inserts themselves into the wrong positions of the DNA. When this kind of incident occurs, the area of where the virus has inserted itself to the cell may start uncontrollable growth. In other words, due to a fail in transporting the functional gene to the defective cells, a tumor might start to grow, or an existing tumor might become worse. Furthermore, scientists and researchers have also discovered that an occurrence where in the new gene of the virus vector successfully enters the correct targeted cells, however the genes might not be able to function and thus it has failed. 

Furthermore, another limitation is unwanted side effects. These side effects include unwanted immune system reactions and infections caused by the virus. The human body will possibly reject the new functional gene in the vectors, our body might view them as aliens and invaders therefore the cells of the body will protect themselves and attack the foreign genes. On the other hand, it is also possible for hemophilia patients who utilize gene therapy, particularly using viral vectors as a cure to get infected by the virus itself. Although researchers, scientists and doctors have removed the harmful DNA of the virus, there is a probability that the virus retrieve back its original state, thus infecting the patient instead of being cured.  

Moreover, there are some factors that might affect the development of gene therapy. These factors are mostly related to ethics and moral issue. People tend to believe that when gene therapy becomes known, researchers may start to have the same aim as genetic engineering through the use of gene therapy. Although the two are quite similar and involves the alteration of genes. However gene therapy aims to change the genes in order to cure a genetic defect, on the other, genetic engineering aims to modify and enhance the genes in order to improve human capabilities to more than normal. Society fears that normal and common characteristics of people will be considered as ‘subnormal’ and more discrimination among society will occur. Furthermore, another issue is concerned with money. This extremely common issue explains that gene therapy might be labeled with quite an expensive price, thus the poor is unable to afford the procedure and only the rich is capable of getting the treatment and getting cured.

I strongly believe that gene therapy is extremely beneficial to society and has the capability to cure patients with genetic diseases. However, at the same time, I also agree on the ethical issue mentioned above. As this world progresses, technology is improved, particularly gene technology on genetic disorders and defects. Once researchers have fulfilled their current goal, they begin to search for another. In other words, I do agree that the aims of gene therapy might change, but instead, it might worsen the society. If gene therapy is successful in eliminating any inherited genetic disease, there is big possibility that researchers and scientists may use it as a means to enhance humanity. They will continue their research, however alter the reason of utilizing gene therapy. I fear that if they do so, parts of society will start bad-mouthing and criticizing each other and the world will have even more problems. 

In conclusion, gene therapy can be considered as a treatment that can be of great use in the future, however, at the same time, it can be viewed as a future treatment that can worsen discrimination in society. This particular treatment had its benefits and limitations. It can cure genetic diseases and other incurable diseases. In particular, it is a revolutionary treatment towards hemophilia patients. They can have an increase in the clotting factors they lack, and will recover faster. However, at the same time, since its still in the process of research and experimentations, it is still harmful to society and can further harm one’s life.

Bibliography:

Websites:

-        - "How Does Gene Therapy Work?" Genetics Home Reference. N.p., n.d. Web. 20 Oct. 2014. <http://ghr.nlm.nih.gov/handbook/therapy/procedures>.

-        - "The Clotting Problem in Hemophilia." - Canadian Hemophilia Society. N.p., n.d. Web. 8 Oct. 2014. <http://www.hemophilia.ca/en/bleeding-disorders/hemophilia-a-and-b/the-clotting-problem-in-hemophilia/>.

-        - "Gene Therapy - Better Health Channel." Better Health Channel. N.p., n.d. Web. 06 Oct. 2014. <http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Gene_therapy>.

-        - "Gene Therapy." Risks. N.p., n.d. Web. 19 Oct. 2014. <http://www.mayoclinic.org/tests-procedures/gene-therapy/basics/risks/prc-20014778>.

-        - "Hemophilia." ASGCT. N.p., n.d. Web. 8 Oct. 2014. <http://www.asgct.org/general-public/educational-resources/gene-therapy-and-cell-therapy-for-diseases/hemophilia>.

-        - "Gene Therapy: The Basics." Cancer Resources. N.p., n.d. Web. 16 Oct. 2014. <http://www.oncolink.org/treatment/article.cfm?c=15&id=323>.

-       -  "Gene Therapy." Risks. N.p., n.d. Web. 19 Oct. 2014. <http://www.mayoclinic.org/tests-procedures/gene-therapy/basics/risks/prc-20014778>.

-        Rocholl, Brandi. "Gene Therapy: Revolutionizing Medicine." N.p., n.d. Web. 19 Oct. 2014. <http://www.ndsu.edu/pubweb/~mcclean/plsc431/students/brandi.htm>.

-        - "Non-Viral Delivery Systems in Gene Therapy." N.p., n.d. Web. 20 Oct. 2014. <http://www.intechopen.com/books/gene-therapy-tools-and-potential-applications/non-viral-delivery-systems-in-gene-therapy>.

-        - "Non-Viral Vectors." Gene Therapy Net.com. N.p., n.d. Web. 21 Oct. 2014. <http://www.genetherapynet.com/non-viral-vectors.html>.

-        - "Gene Therapy Viral Vectors Explained." Gene Therapy Viral Vectors Explained. N.p., n.d. Web. 21 Oct. 2014. <http://www.genetherapynet.com/viral-vectors.html>.

-        - "Gene Therapy." Genetics Home Reference. N.p., n.d. Web. 21 Oct. 2014. <http://ghr.nlm.nih.gov/handbook/therapy?show=all>.
         - "Hemophilia." Symptoms. N.p., n.d. Web. 23 Oct. 2014. <http://www.mayoclinic.org/diseases-conditions/hemophilia/basics/symptoms/con-20029824>.

Books:

-     - Fauci, Anthony S. Harrison's Principles of Internal Medicine, 14th Edition. New York: McGraw-Hill, Health Professions Division, 1998. Print.

-     -    Beutler, Ernest, and William Joseph Williams. Hematology. New York: McGraw-Hill, 1990. Print.

      - Snedden, Robert. DNA & Genetic Engineering. Chicago, IL: Heinemann Library, 2008. Print.