Gene Therapy: A Promising Future for Type 1 Diabetes Mellitus Patients

Over the past years, the rates of incidence of type 1 diabetes continue to rise around the world, especially in China, India, and the United States. It is a major cause for kidney failure, blindness, stroke, and heart attacks. Statistics have shown that 1.6 million deaths in 2016 were directly caused by diabetes (“Diabetes”). Fortunately, gene therapy, an experimental scientific technique, can provide a favorable solution to this problem. By introducing an insulin-producing gene into non-beta cells in the patients’ pancreas, insulin gene therapy might be able to permanently cure one of the world’s most common diseases today.

Different from type 2 diabetes or gestational diabetes, patients with type 1 diabetes are childhood-onset and require chronic administration of insulin (“Diabetes”). Their pancreas’ insulin production is deficient because their immune system falsely attacks the β cells within their pancreas which are used to secrete and synthesize proteins like insulin. This then causes their disability to penetrate the ingested glucose into their cells (Albert, 2018). According to the ADA, over 1.25 million people in the United States are diagnosed with this unpreventable, and if untreated, fatal disease (Timmons, 2018). Without their daily administration, type 1 diabetes patients don't produce any insulin and thus can soon experience severe symptoms including thirst, extreme hunger, weight loss, vision changes, and intense fatigue (“Type 1 diabetes”). 

Fortunately, insulin gene therapy, an alternative strategy, might soon be able to replace the flawed treatments for type 1 diabetes used nowadays, which is daily insulin injections and pancrea transplant. Gene therapy generally refers to the therapeutic process of introducing genetic material into cells to produce beneficial proteins and compensate abnormal genes (“What is Gene Therapy?”). Vectors, a type of carrier that is genetically engineered to transport genes, are used to insert the gene into a specific tissue of the patient’s body, where it will make new, functioning protein if the treatment is successful.  However, insulin gene therapy is a more specific treatment that targets type 1 diabetes patients. Since the patients’ symptoms are caused by their immune system destroying the insulin-producing β cells, scientists are taking a new approach to reprogramme non-β cells, which are not attacked, into surrogate β cells that can restore insulin production. In theory, by creating new cells or overexpressing β cell-specific transcription factors including PDX1, NeuroD1, Neurog3, Pax4, Pax6, Nkx6.1, Nkx2.2, and MafA in non-β cells using cytomegalovirus (CMV) promoters, the new surrogate cells should be able to synthesize an adequate amount of insulin in response to the current blood glucose levels and store them in secretory granules like native β cells (Handorf et al., 2016). Adding on, the current primary therapeutic targets for this treatment are pancreatic alpha cells, hepatocytes, and the small intestine and hypothalamus cells due to their special characteristics (“Gene Therapy for Type 1 Diabetes Aims to Eliminate Daily Insulin Injections”). Not only can healthy native β cells sense and respond to minor changes in blood glucose levels effectively, they can also perfectly control insulin biosynthesis. Only cells mentioned above have innate glucose-responsiveness and can express glucokinase and GLUT2, allowing them to complete the same tasks and therefore also making them suitable for surrogate β cells (Handorf et al., 2016). Major progress has already been made on this treatment as Dr. George Gittes’s researcher team successfully restored insulin production in a mouse model in 2017 (Steer, 2018). By delivering two transcription factors, PDX1 and MafA, using a vector named adeno-associated viral (AAV) into the mouse’s abundant pancreatic alpha cells, the researchers were able to transform them into insulin-producing β cells and maintain normal blood glucose level in the mouse for four months, which transfers to few years on humans (Nichols, 2018) (Rocco, 2011). 

There are many strengths towards this solution; for instance, as major advances were made, it can solve various problems by providing a feasible and promising treatment to largely reduce the number of deaths, which reached 1.6 million in 2016 and will continue to increase in the future as predicted by scientists. Once the research is done, it can also reduce the damage cost, since the estimated cost due to consequently reduced productivity caused by diagnosed diabetes reached 90 billion in 2017 (Timmons, 2018). Combining these two factors together, finding a permanent cure for this disease is unarguably necessary. Furthermore, insulin gene therapy is more effective and long-lasting than any other treatments used nowadays. As shown by the mouse model, the patients’ blood glucose level can possibly remain normal (less than 100 mg/dL) for a few years, and even longer in the future, without their daily insulin injections, providing great safety and convenience to the patients’ lives (Whiteman, 2017). 

However, despite the strengths, there are also some deficits in this solution. Compared to current treatments, gene therapy is relatively expensive to both research and implement. Billions of dollars have already been spent on the study of this treatment, and more money is likely going to be inputted into this field. The most inexpensive treatment in this field now also costs more than two-hundred thousand dollars, which aren’t affordable for many people (Mullin, 2017). Another weakness is that it’s at risk of getting adapted by nature just like how antibiotics are already working less effectively within less than a century. Scientists predict that gene therapy might also reverse itself after the treatment is stopped and be resisted by patients’ bodies after a few generations (Regoli, 2019).

If looked from a unique perspective, this solution is in relation with various social issues. With the predicted treatment cost being so high, there will be many patients in developing and even developed countries who can’t afford the operation and thus in danger of death and other severe consequences. For example, an average Canadian’s annual income is around fifty-seven thousand dollars, after reducing the necessary expenses, it will take them more than 20 years to save up enough for the treatment (Randall, 2019). Compared to those who are wealthy enough, most people don’t have the equal opportunity and access to these advanced treatments, posing inevitable problems and arguments about equality and human rights (Hunt, 2008). Whether or not to include insulin gene therapy in future health care insurance is also an issue to argue with for many countries because of the uncertainty, risks, and high cost of the treatment (Regoli, 2019).

Overall, insulin gene therapy poses a promising method towards solving the problems of type 1 diabetes patients. As an alternative treatment, it can reprogram non-β cells into surrogate β cells that have the same ability as native β cells, which replaces inconvenient daily injections. However, while it seems to be a perfect solution with its effectiveness, there are still various flaws and problems posed by this therapy, including concerns about risk and social issues that need to be gradually solved as this technology becomes more advanced in the future.

Works Cited

“Cheese-Producing Bacteria Could Help Reverse Type 1 Diabetes.” Labiotech.eu, 5 Sept. 2019, www.labiotech.eu/medical/actobio-type-1-diabetes-bacteria/.

“Diabetes.” World Health Organization, World Health Organization, www.who.int/news-room/fact-sheets/detail/diabetes.

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

“Gene Therapy for Type 1 Diabetes Aims to Eliminate Daily Insulin Injections.” UW School of Medicine and Public Health, www.med.wisc.edu/news-and-events/2013/july/gene-therapy-for-type-1-diabetes/.

Handorf, Andrew M, et al. “Insulin Gene Therapy for Type 1 Diabetes Mellitus: Unique Challenges Require Innovative Solutions.” IntechOpen, IntechOpen, 18 May 2016, www.intechopen.com/books/modern-tools-for-genetic-engineering/insulin-gene-therapy-for-type-1-diabetes-mellitus-unique-challenges-require-innovative-solutions.

Handorf, Andrew M, et al. “Insulin Gene Therapy for Type 1 Diabetes Mellitus.” Experimental and Clinical Transplantation : Official Journal of the Middle East Society for Organ Transplantation, U.S. National Library of Medicine, Apr. 2015, www.ncbi.nlm.nih.gov/pubmed/2589.

“How Does Gene Therapy Work? - Genetics Home Reference - NIH.” U.S. The National Library of Medicine, National Institutes of Health, ghr.nlm.nih.gov/primer/therapy/procedures.

Hunt, Sonia. “Controversies in Treatment Approaches: Gene Therapy, IVF, Stem Cells, and Pharmacogenomics.” Nature News, Nature Publishing Group, 2008, www.nature.com/scitable/topicpage/controversies-in-treatment-approaches-gene-therapy-ivf-792/.

Mullin, Emily. “Gene Therapy May Soon Be More Affordable.” MIT Technology Review, MIT Technology Review, 24 Oct. 2017, www.technologyreview.com/s/609197/tracking-the-cost-of-gene-therapy/.

Nett, Philipp C., et al. “Hepatic Insulin Gene Therapy in Insulin‐Dependent Diabetes Mellitus.” Wiley Online Library, John Wiley & Sons, Ltd (10.1111), 11 Aug. 2003, onlinelibrary.wiley.com/doi/full/10.1046/j.1600-6143.2003.00221.x.

Nichols, Hannah. “Diabetes: Can Gene Therapy Normalize Blood Glucose Levels?” Medical News Today, MediLexicon International, www.medicalnewstoday.com/articles/320544.php#1.

Randall, Steve. “How Much Does the Average Canadian Save?” Wealth Professional, Wealth Professional, 28 Mar. 2019, www.wealthprofessional.ca/news/industry-news/how-much-does-the-average-canadian-save/255921.

Regoli, Natalie. “14 Advantages and Disadvantages of Gene Therapy.” ConnectUS, 27 Feb. 2019, connectusfund.org/14-advantages-and-disadvantages-of-gene-therapy.

Rinkesh. “Pros and Cons of Genetic Engineering.” Conserve Energy Future, 9 Dec. 2017, www.conserve-energy-future.com/pros-and-cons-of-genetic-engineering.php.

Steer, Isobel. “Gene therapy temporarily halts type 1 diabetes in mice.” BioNews, 8 Jan. 2018, www.bionews.org.uk/page_96307\.

Timmons, Jessica. “Diabetes: Facts, Statistics, and You.” Healthline, Healthline Media, 20 Aug. 2018, www.healthline.com/health/diabetes/facts-statistics-infographic#1.

“Type 1 Diabetes Statistics.” Beyond Type 1, beyondtype1.org/type-1-diabetes-statistics/.

“Type 1 Diabetes.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 7 Aug. 2017, www.mayoclinic.org/diseases-conditions/type-1-diabetes/symptoms-causes/syc-20353011.

Whiteman, Honor. “Type 1 Diabetes Cured in Mice Using Gene Therapy.” Medical News Today, MediLexicon International, 8 May 2017, www.medicalnewstoday.com/articles/317343.php#1.