Login

Join for Free!
116934 members

Biology Articles » Immunobiology » Edmonton Protocol - Possible cure for Type 1 Diabetes patients

Edmonton Protocol - Possible cure for Type 1 Diabetes patients

Abstract

The Edmonton Protocol is only capable of treating patients with Type 1 Diabetes since they lack the appropriate cells. Patients with Type 2 Diabetes have normal immune system behavior and islet cells, but the affectivity of insulin has diminished. The procedure starts with the isolation of islet cells from cadaverous donors. These are isolated through an enzymatic solution called Liberase. The amount of islets collected may not be enough, and typically more than one source is needed. Fewer and fewer islet cells are being needed for implants due to other advancements in the protocol. However once a sufficient number of islets are collected, they are then inserted into the circulatory system in between the heart and the capillary beds. This replaces the beta cells that were killed by the patient’s immune system; however it does not by itself cure the patient. As mentioned earlier, the patient is then treated with a series of drugs that suppress the immune system known as immunosuppressants. Advancements in these immunosuppressants make it possible for few islets to be used, which makes the process easier and less expensive. The Edmonton Protocol looks promising as a potential cure for Type 1 Diabetes.

Introduction

Diabetes is a disease that causes hyperglycemia, or high blood-sugar levels. Diabetes affects over 171 million people worldwide. There are 3 types of diabetes, but this will focus on mainly Type 1 Diabetes (formerly known as Juvenile Diabetes) which has several genetic components to it. The disease is characterized by the lack of insulin in the blood stream. Insulin is a protein that carries glucose to cells that is needed for energy. In Type 1 Diabetes, this is usually hindered due to an autoimmune reaction which destroys the cells that produce insulin. These cells are located in the pancreas, specifically the endocrine glands called “islets of Langerhans”, but more specifically beta cells. When insulin isn’t present in sufficient quantities, blood-sugar concentration levels increase, which causes hyperglycemia. Hyperglycemia causes severe fatigue, dehydration, and even impotence. Currently, the typical treatment for diabetes is insulin supplemented intravenously. This requires careful regulation of carbohydrate intake, and can be a nuisance. A medical procedure called the “Edmonton Protocol” implants islets in patients to produce insulin. The procedure is relatively new with the first procedure taking place in 1999. The Edmonton Protocol looks very promising in the future, and deserves a closer look.

Discussion

Currently, the only treatment for diabetes is insulin taken either intravenously or through an automated pump. Either method is a hassle to the patient and requires very careful monitoring of diet. Some foods are completely off limits to people with diabetes even with insulin. Taking too much or too little can cause serious problems. Researchers have been toying with the idea of pancreatic transplants, or transplants of the islet cells within them. The method with the most promise was developed in 1999 and is named after Edmonton, Canada, the city where it was researched.

There have been stunning advancements over recent years in the Edmonton Protocol. Uses of cooling devices to keep the pancreas at an optimal temperature have greatly increased the number of viable islets (Nagata et al, 2006). This procedure is used on Non-Heart Beating Donors (NHBDs) who are pronounced brain-dead and are capable of being harvested for islets. A cooling device is placed in situ in order to prevent overheating. New techniques for the enzymatic digestion are being developed which shorten the isolation time which allows for the islets to be collected faster, giving less time for warming. This also exposes the islets to the enzymes for a shorter amount of time, since new studies seem to show that exposure to the enzymatic isolation process can decrease the amount of insulin secreted (Balamurugan, 2003). Time is a huge factor in successful harvesting. Not only does collection in a timely matter yield more islets, but it also increases the affectivity of the islets that are harvested. Currently, one of the biggest issues regarding Edmonton Protocol is the collection of the islets. It takes too many donors to make the procedure readily available. Leading researchers are focusing mainly on how to increase islet yield so that one donor may be able to supply even more than 1 patient. It has also been suggested that enough islet cells can be implanted that will guard against severe hyperglycemia as an alternative to curing it all together.

It was once believed that the immunosuppressants used to keep the islets from being rejected may cause kidney failure; however no correlation between the concentrations of kidney failure and immunosuppressants were found (Andres, 2005). Research is being done to alter the concentrations of immunosuppressants, and when treatment with them should occur (Sato, 2006). The current immunosuppressants used are Sirolimus and Tacrolimus. These are necessary to protect the implanted islets from the antibodies that the patients produce. As stated earlier, Type 1 diabetes is caused by an autoimmune disease, this means that the patient produces these antibodies that destroy the islets. Without the drugs, the patient’s immune system would kill the transplanted islets again, rendering the patient insulin-dependant. There has been a huge increase in success of this procedure. In the first years of islet transplantation, the success rate (those who were insulin-independent after 1 year) was about 14% (Bucher, 2003).. When the Edmonton Protocol was developed in 1999, it raised the success rate to 80%

(Shapiro, 2006). These numbers however drop off when you look at insulin-independence a few years after treatment. The insulin-dependence is caused by the degradation of the transplanted islets due to the ineffectiveness of the immunosuppressants being used. Further research has to be done on new immunosuppressants and the application of the immunosuppressants, but researchers must keep an eye on kidney function.

However even after insulin-independence is lost, long lasting effects of the islets were still noticeable. The transplanted islets still provided protection against severe hypoglycemia. This could prevent dehydration and severe fatigue, and even death in some patients. This can lower the impact of being diagnosed with diabetes and be a strong psychological boost for treatment. The islets also retain a higher level of glycosylated hemoglobin. This means that blood-sugar levels are still normal. Insulin treatment can be less of a constant regiment, which also provides a stronger psychological boost that the patient isn’t hindered severely or has to monitor the levels closely (Shapiro, 2006).

Conclusion

The Edmonton Protocol looks very promising as a cure for Type 1 diabetes. Even without sustaining insulin-independence the benefits of the transplant still greatly helps the patient’s body, as well as his psyche. There has been speculation of kidney failure associated with the procedure however it seems much safer than originally believed. The two efficiency factors occurs at cell harvesting and the immunosuppressants used. Shortening the exposure time while harvesting the donors seems to increase islet yield and productivity. Varying the concentrations of immunosuppressants used also seems to increase the survival of the islet cells. In a very short period of time, the advancements in the Edmonton Protocol are able to give hope and easier living to people with Type 1 Diabetes.

References

Andres, A, Toso C, Morel P, Demuylder-Mischler S, Bosco D, Baertschiger R, Pernin N, Bucher P, Majno PE, Buhler LH, Berney T.. "Impairment of renal function after islet transplant alone or islet-after-kidney transplantation using a sirolimus/tacrolimus-based immunosuppressive regimen.." Transplant international 11(2005): 1226-30.

Balamurugan AN, Bottino R, Giannoukakis N, Smetanka C. "Prospective and challenges of islet transplantation for the therapy of autoimmune diabetes.." Pancreas 32(2006): 231-43.

Bucher, P, Mathe Z, Bosco D, Andres A, Buhler LH, Morel P, Berney T.. "Islet of Langerhans transplantation for the treatment of type 1 diabetes.." Swiss Surgery 9(2003): 242-6.

Nagata, H, Matsumoto S, Okitsu T, Iwanaga Y, Noguchi H, Kinukawa T . "Procurement of the human pancreas for pancreatic islet transplantation from marginal cadaver donors.." Transplantation 82(2006): 327-31.

Sato, E, Shimomura M, Masuda S, Yano I, Katsura T, Matsumoto S, Okitsu T, Iwanaga Y, Noguchi H, Nagata H, Yonekawa Y, Inui K.. "Temporal decline in sirolimus elimination immediately after pancreatic islet transplantation.." Drug metabolism and pharmacokinetics 21(2006): 492-500.

Shapiro, AM, Ricordi C, Hering BJ, Auchincloss H. "International trial of the Edmonton protocol for islet transplantation.." The New England Journal of Medicine 355(2006): 1318-30.

 

Contributed by: EmmVeePee


rating: 5.33 from 9 votes | updated on: 26 Aug 2007 | views: 5205 |

Rate article:







excellent!bad…