- Edmonton protocol
The Edmonton Protocol is a method of implantation of pancreatic islets for the treatment of
type 1 diabetes mellitus , specifically "brittle" type 1 diabetics prone to hypoglycemic unawareness. The protocol is named for the islet transplantation group at theUniversity of Alberta in the Canadian city ofEdmonton , where the protocol was first devised in the late 1990s.Procedure
The Edmonton Protocol involves isolating islets from a cadaveric donor
pancreas using a mixture ofenzymes called Liberase™ (Roche). Each recipient receives islets from one to as many as three donors. The islets are infused into the patient'sportal vein , and are then kept from being destroyed by the recipient'simmune system through the use of twoimmunosuppressants ,sirolimus andtacrolimus as well as a monoclonalantibody drug used in transplant patients calleddaclizumab .History
Islet isolation and transplantation was pioneered by
Paul Lacy throughout the 1960s. He and Walter Ballinger together were able to restore normoglycaemia in diabeticrat s following the transplantation of isolated islets into the rodent's livers. Scientists have not yet successfully translated Dr. Lacy's success in rodents to humans.The Edmonton Protocol was primarily developed by Dr
James Shapiro (transplant surgeon), Jonathan Lakey Ph.D., Dr Edmond Ryan (endocrinologist), Gregory Korbutt Ph.D., Dr. Ellen Toth, Dr. Garth Warnock, Dr. Norman Kneteman, and Ray Rajotte Ph.D., at the University of Alberta Hospital and the Surgical-Medical Research Institute. The first patient was treated using the Edmonton Protocol in March 1999. The protocol was first published in theNew England Journal of Medicine in July 2000 .The NEJM report was exciting for the diabetes field because all seven patients undergoing the Edmonton Protocol remained
insulin -independent after an average of 12 months.Current review
It has recently been reported that of thirty-six patients transplanted, only sixteen (44%) were insulin-independent after one year; ten (28%) had partial graft function after one year; and ten (28%) had complete graft loss after one year. Insulin independence is not usually sustainable in the long term, but the transplanted islets still function enough to provide protection from severe hypoglycemic episodes and unawareness.
The major problem limiting islet transplantation therapy for type 1 diabetic individuals is the lack of organ donors.
References
* [http://content.nejm.org/cgi/content/abstract/343/4/230] Shapiro AMJ, Lakey JRT, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343:230-238.
* [http://ajp.amjpathol.org/cgi/content/full/167/2/299] Saffitz JE, Schmidt RE, McDaniel ML. Dr. Paul Eston Lacy, 1924–2005. American Journal of Pathology. 2005;167:299-300.
* [http://diabetes.diabetesjournals.org/cgi/content/full/54/7/2060] Ryan EA, Paty BW, Senior PA, Bigam D, Alfadhli E, Kneteman NM, Lakey JR, Shapiro AM. Five-year follow-up after clinical islet transplantation. Diabetes. 2005 Jul;54(7):2060-9.
* [http://www.springerlink.com/(ovlfajnembfllk4510btjnzu)/app/home/contribution.asp?referrer=parent&backto=issue,18,26;journal,62,227;linkingpublicationresults,1:101185,1] Sutherland DE, Gruessner RW, Gruessner AC. Pancreas transplantation for treatment of diabetes mellitus. World J Surg. 2001 Apr;25(4):487-96.
* [http://content.nejm.org/cgi/content/abstract/355/13/1318] Shapiro AMJ, Ricordi C, Hering BJ et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006;355:1318-1330.
* [http://www.transplantjournal.com/pt/re/transplantation/abstract.00007890-200509270-00014.htm] O'Gorman D, Kin T, Murdoch T, Richer B, McGhee-Wilson D, Ryan EA, Shapiro AMJ, Lakey JRT. The standardization of pancreatic donors for islet isolations. Transplantation. 2005 Sep;80(6):801-806.External links
* [http://www.islet.ca Clinical Islet Transplant Program - University of Alberta]
Organ transplantation
[https://web.emmes.com/study/isl/]
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