Is Gene Therapy Truly Therapeutic

Rohit Patel

12/11/2023

Professor Horgan

Seminar of Science Writing

Is Gene Therapy Truly Therapeutic

 

                Imagine you have retinitis pigmentosa? What is that, you may ask? I think the best way for me to explain is by putting you in the shoes of someone with retinitis pigmentosa. Let’s place you in the open fields looking at the snow-capped mountains of the Swiss Alps. You are mesmerized by the beauty of the landscape you are encompassed by. The slight breeze blowing in the air creates a rustling sound with the grass. The tall mountain peaks reach the upper limits of our atmosphere. Now imagine, if you took a PVC pipe and put it in front of your eyes and are now looking through this narrow pipe. Your field of vision is much more constrained. All you can see now is just the fields or just the mountains. It requires you to move your head around to even get a chance to see both separately. Now imagine that this PVC pipe gets narrower…and narrower…and narrower. Your field of vision is so minuscule that you can’t even see the full landscape anymore and can only see small glimpses of it. This, my friends, is retinitis pigmentosa. Retinitis pigmentosa is a type of eye disease where your retina is damaged. The cells in your retina are slowly breaking down over time which leads to a loss of vision. This condition is considered to be a genetic condition. Imagine barely being able to experience the vast world and being restricted due to this, and there was nothing you could do about that. However, in your narrow field of vision, you see a light. The light gets even brighter. This light is gene therapy and is the answer you were looking for to fix all the pain you have been feeling with the lack of vision. However, there are some people who have perfect vision, yet they can’t seem to see the true therapeutic powers of gene therapy and are blinded by misconceptions.

                For starters, I have barely heard about gene therapy until coming to college. I think that it needs to be added to high school curriculums so more people have exposure to the concept of it earlier on. However, what I want to do now is to change the minds of those who doubt the power of gene therapy. So, what is gene therapy, you may ask? Gene therapy is a treatment that has risen to action in the past few decades and has the ability to treat certain genetic conditions and some other medical conditions. That is right. It has the ability to potentially cure GENETIC conditions!

 So how does it work, you may ask. Gene Therapy can work in 3 ways. There is the inhibition of a gene, the augmentation of a gene, as well as just killing cells that can cause a disease. Starting off with gene inhibition, there may be a cell that has this gene that is faulty. What gene therapy would do in gene inhibition therapy would be to take this gene, known as a blocking gene, and then integrate this gene into the cell. This new gene will then block the faulty gene, and the cell will regain its normal function. Within gene augmentation therapy, there may be a cell that has a gene that isn’t functioning. What the therapy would do is then add this gene that is functioning and augment the cell so that it functions normally. Lastly, there is the therapy, where the cells that cause the disease are killed. This can be done in 2 ways. One will involve taking this gene, known as a suicide gene, and having it integrated into a cell that is diseased. The suicide gene will lead to the production of toxic materials, which will kill the diseased cell. The other way that the diseased cell can be killed can be done using the implementation of a marker gene where when the gene is integrated into the cell, marker proteins will be expressed on the surface of a cell. This marker will show the immune system that the cells need to be killed. As a result, the immune system will attack the cell, and the diseased cell will die. This was the basic way of explaining gene therapy. A lot of you might have had misconceptions about gene therapy previously, and this might have helped convert you into a believer in gene therapy. However, I know that there are still some people who are against gene therapy. 

One of the reasons that they might give is that gene therapy is too expensive. According to iiste.org, “Gene therapy prices range from $373,000 for a single dose of CAR-T therapy Yescarta to $2.1 million for Zolgensma”. Yescarta is a medication for non-Hodgkin lymphoma, and Zolgensma is a treatment for spinal muscular atrophy. I must admit that this is pretty expensive. However, what you need to consider from this is that gene therapy is, in most cases, just one treatment. It is not like chemotherapy, where you might have to go for multiple hospital visits and feel all the painful side effects. What you have to always have in the back of your mind, however, is that with just one treatment, you can potentially cure your cancer or have the ability to live a normal and independent life for the cases of lymphoma and spinal muscular atrophy, respectively. In terms of insurance coverage for gene therapy, it does vary depending on which insurance plan you are on. There are some plans that might outright cover the cost, while there are plans that require you to first go through cheaper forms of treatment and then, if those don’t work, will cover gene therapy as a last resort.  People also say it is fairly new and that it is risky. The field of gene therapy is fairly new and has been around for a few decades. But research is constantly being done, and gene therapy is getting safer and more powerful every day. There are a ton of clinical trials being done, and everything is highly monitored with astronomically high standards. There are also ethical concerns. Because it involves editing genes, there could be ethical concerns. In genes, there are the somatic cells or the body cells, and then there are the sex or the germ cells. Gene therapy focuses on the body cells, and these body or somatic cells are genetically altered. These alterations to the somatic cells cannot be passed down to children or offspring. However, there are gene therapies that also target the germ cells, which can be passed down to children. So that is one thing people fail to consider. There is gene therapy for somatic cells and gene therapy for germ cells. In addition, it is considered illegal to perform germline gene editing.

Gene therapy can have long-term effects with just one treatment. Because genes are edited, the functions are changed, which means that there can be long-term effects. In germline gene therapy, there is also the benefit of passing on good genes. You may have had a genetic condition, but if your genes were edited and your condition was cured. If this change was a germline change, you will be able to pass down the good version of your genes so that your offspring don’t get the genetic condition. In addition, gene therapy is constantly advancing and improving. Gene therapy is getting safer and more powerful and is being able to be used in more diseases.

                Despite me saying all of these benefits and corrections to misunderstandings regarding gene therapy, there will still be someone who says, “Well, what about Jesse Gelsinger”? For those who don’t know, Jesse Gelsinger was a person who was a victim of a rare situation where gene therapy had “gone wrong.” Jesse Gelsinger had a condition known as ornithine transcarbamylase deficiency. In this condition, ammonia can reach levels where it can kill a person. The way he was able to manage his condition was by going on a low-protein diet and taking 50 pills a day. However, there was one day when he was 17 when Jesse’s father found Jesse on the couch and vomiting in an uncontrollable manner. This all happened because he didn’t take his medicine regularly anymore. As a result, he had to be put into an induced coma and had to be intubated. Then one day, the opportunity for gene therapy came up for Jesse Gelsinger, and he took the opportunity; however, after going through it, he was considered to be brain-dead and had life support taken off. One thing that has to be considered in this case, however, was that the study was meant to study for safety. At the time, the study was focused on being able to move the treatments to serve babies with the condition, and the study was not intended to improve the health of the participants. Despite knowing this, Jesse wanted to help. What is important to note is that this incident was a big setback for the scientists involved as well as the realm of gene therapy. I must admit that this piece of evidence is a harrowing tale of the dark side of gene therapy, and it can dissuade many of you from even considering it. People who were part of the study for Jesse Gelsinger were punished, and gene therapy became like a black label, according to sciencehistory.org. Ever since the incident, with tons of research, the field of gene therapy has become safer.

                Let me try to give you a 180 on the Jesse Gelsinger case and provide you an example of gene therapy being very powerful. Let’s look at Sickle cell and how gene therapy was used to combat sickle cell. As many people know, Sickle cell anemia affects millions of people worldwide. According to healthdata.org, “The number of people living with sickle cell disease globally increased by 41·4% (38·3–44·9), from 5·46 million (4·62–6·45) in 2000 to 7·74 million (6·51–9·2) in 2021”. Sickle cell anemia is caused by a genetic condition where your red blood cells become more of a shape of a “C” rather than a round cell. The red blood cells also become stickier and harder. In sickle cell anemia, there could be a reduction in healthy red blood cells, and sickled cells can even block blood flow. To combat the condition, certain pharmaceuticals have been using the CRISPR-Cas9 System to perform gene therapy. One pharmaceutical company in particular, Vertex Pharmaceuticals, has been using this CRISPR-Cas9 System to boost the levels of healthy fetal hemoglobin in the blood. Before, some patients had to get blood transfusions to have healthy blood in their bodies, but after the gene therapy, some patients didn’t need blood transfusions anymore. These patients were able to live more free lives. In addition to the work at Vertex Pharmaceuticals, there have been two treatments that were recently approved by the FDA to combat Sickle Cell Disease. The treatments are known as Casgevy and Lyfgenia. They both can be used on patients who are aged 12 and older. According to Peter Marks, M.D., Ph.D., ““These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health…Today’s actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDA’s commitment to facilitating the development of safe and effective treatments for conditions with severe impacts on human health”. These were major advances to the gene therapy field, considering the past with the incident of Jesse Gelsinger.

                Gene therapy is a very powerful treatment, yet not many people know about it or even disregard it by honing in only on the cons. With advances rapidly occurring, success has already been shown in treating leukemia, hemophilia, and blindness from retinitis pigmentosa. In the future, it may also be able to treat cystic fibrosis or sickle cell disease completely. While the cons are something to consider, especially the cost, gene therapy is something that can change your life around with just “one doctor’s visit”.

 

Works Cited:

Daley, Jim. “Four Success Stories in Gene Therapy.” Scientific American, 11 May 2022, www.scientificamerican.com/article/four-success-stories-in-gene-therapy/.

Diaconescu, Adrian. “Pros and Cons of Gene Therapy.” Academic Hosting & Event Management Solutions, International Knowledge Sharing Platform, 27 June 2022, www.iiste.org/pros-and-cons-of-gene-therapy/.

“Gene Therapy.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 29 Dec. 2017, www.mayoclinic.org/tests-procedures/gene-therapy/about/pac-20384619.

“Genetic Therapies Benefits and Risks.” National Heart Lung and Blood Institute, U.S. Department of Health and Human Services, 24 Mar. 2022, www.nhlbi.nih.gov/health/genetic-therapies/benefits-risks#:~:text=In%20the%20future%2C%20genetic%20therapies,cancers%20or%20infections%2C%20including%20HIV.

Gragnolati, Amy B. “What Are the Advantages and Disadvantages of Gene Therapy?” Edited by Sophie Vergnaud, GoodRx, GoodRx, 17 Feb. 2022, www.goodrx.com/health-topic/gene-therapy/gene-therapy-pros-cons.

Pflaum, Carly. “FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease.” U.S. Food and Drug Administration, FDA, 8 Dec. 2023, www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease.

Rinde, Meir. “The Death of Jesse Gelsinger, 20 Years Later.” Science History Institute, 1 June 2023, sciencehistory.org/stories/magazine/the-death-of-jesse-gelsinger-20-years-later/.

Thomson, Azalea, et al. “Global, Regional, and National Prevalence and Mortality Burden of Sickle Cell Disease, 2000–2021.” The Institute for Health Metrics and Evaluation, IHME, 15 June 2023, www.healthdata.org/research-analysis/library/global-regional-and-national-prevalence-and-mortality-burden-sickle-cell#:~:text=The%20number%20of%20people%20living,9%C2%B72)%20in%202021.

Warmflash, Dr. David. “Gene Therapy: What Is It and How Does It Work?” LiveScience, Purch, 23 Mar. 2023, www.livescience.com/gene-therapy-everything-you-need-to-know-about-the-dna-tweaking-treatments.

“What Is Gene Therapy?” @yourgenome · Science Website, 21 July 2021, www.yourgenome.org/facts/what-is-gene-therapy/.