Curing Type 1 Diabetes with Gene Therapy

Type 1 diabetes mellitus (sometimes called insulin-dependent diabetes) is a chronic disease that occurs when the pancreas produces little or no insulin. People with this form of diabetes require injections of insulin every day to control the glucose levels in their blood, or they will die.

In 2011 the International Diabetes Federation estimated more than 350 million people worldwide suffered from diabetes and expected an increase to more than 550 million people by 2030. Type 1 diabetes accounts for approximately 5% of all cases of diabetes and it is estimated that 78 000 children develop type 1 diabetes every year.

Insulin replacement by needle injection and subcutaneous pumps has had a huge impact on extending the lives of millions of patients with diabetes. This solution is not ideal however, as it still typically means a reduced lifespan, intensive disease management, and a high likelihood of developing debilitating complications.

Pancreas transplantation has resulted in insulin independence in most patients during the first year after transplant, but it is also associated with a risk of complications from surgery, as well as long-term immunosuppression treatments. This treatment is normally reserved for patients who also require a kidney transplant.

Another option is transplanting just the cells in the pancreas that produce insulin, which is much less invasive as procedures go (injection of cells under portal vein under local anesthesia). Considered a highly effective therapy inducing sustained insulin independence or reduced insulin requirements in most patients. The only draw backs to this therapy are the shortage of high-quality donor cells, long-term graft failure, and the risks associated with long term immunosuppression.

Gene therapy on the other hand looks to insert a properly functioning version of the insulin producing gene back into your own cells. Thus negating the need for surgery, immunosuppression, and any donor. I first heard of a group out in BC working on this using gut endocrine stem cells (cells in the lining of your gut that reproduce to form various cell types) back in the early 2000’s. The idea being that these cells would be able to detect blood glucose levels and then produce insulin responsively. The group eventually started the company EnGene that now works on a multitude of gene therapy and protein delivery solutions.

Work in this area over the last decade has produce some very promising results in reprogramming liver, gut, and pancreatic cells into insulin producing cells. A group in Spain last month reported they replaced two genes to cure a dog of type 1 diabetes using a similar approach. Although the technology requires more testing before human clinical trials can be started, the continued advancements in this technology provide hope for those searching for a cure to diabetes.

Photo credit: brianjmatis / CC BY-NC-SA

References:

• Fujita Y, Cheung AT, Kieffer TJ. Harnessing the gut to treat diabetes. Pediatr Diabetes. 2004;5 Suppl 2:57-69. The Laboratory of Molecular and Cellular Medicine, Department of Physiology, University of British Columbia, Vancouver, BC, Canada PMID: 15601375
• Tudurí E, Bruin JE, Kieffer TJ. Restoring insulin production for type 1 diabetes. J Diabetes. 2012 Dec;4(4):319-31. Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada. doi: 10.1111/j.1753-0407.2012.00196.x.
• Callejas D, Mann CJ, Ayuso E, Lage R, Grifoll I, Roca C, Andaluz A, Ruiz-de Gopegui R, Montane J, Munoz S, Ferre T, Haurigot V, Zhou S, Ruberte J, Mingozzi F, High K, Garcia F, Bosch F. Treatment of Diabetes and Long-term Survival Following Insulin and Glucokinase Gene Therapy. Diabetes. 2013 Feb 1. Center of Animal Biotechnology and Gene Therapy, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain.