Edmonton protocol
Encyclopedia
The Edmonton Protocol is a method of implantation of pancreatic
islet
s 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 the University of Alberta
in the Canadian
city of Edmonton
, where the protocol was first devised in the late 1990s, and published in The New England Journal of Medicine in July 2000.
pancreas
using a mixture of enzymes called Liberase (Roche). Each recipient receives islets from one to as many as three donors. The islets are infused into the patient's portal vein, and are then kept from being destroyed by the recipient's immune system
through the use of two immunosuppressants, sirolimus
and tacrolimus
as well as a monoclonal antibody
drug used in transplant patients called daclizumab
.
was pioneered by Paul Lacy throughout the 1960s. He and Walter Ballinger together were able to restore normoglycaemia in diabetic rat
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 the New 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.
The major problem limiting islet transplantation therapy for type 1 diabetic individuals is the lack of organ donors.
"Since 2000, Several hundred people have received islet transplants, by a year after transplant, 50 - 68% of patients do not need to receive additional insulin, but by five years after the procedure, few than 10% of total patients are free of daily insulin supplementaition."
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
islet
Islets of Langerhans
The islets of Langerhans are the regions of the pancreas that contain its endocrine cells. Discovered in 1869 by German pathological anatomist Paul Langerhans at the age of 22, the islets of Langerhans constitute approximately 1 to 2% of the mass of the pancreas...
s 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 the University of Alberta
University of Alberta
The University of Alberta is a public research university located in Edmonton, Alberta, Canada. Founded in 1908 by Alexander Cameron Rutherford, the first premier of Alberta and Henry Marshall Tory, its first president, it is widely recognized as one of the best universities in Canada...
in the Canadian
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
city of Edmonton
Edmonton
Edmonton is the capital of the Canadian province of Alberta and is the province's second-largest city. Edmonton is located on the North Saskatchewan River and is the centre of the Edmonton Capital Region, which is surrounded by the central region of the province.The city and its census...
, where the protocol was first devised in the late 1990s, and published in The New England Journal of Medicine in July 2000.
Procedure
The Edmonton Protocol involves isolating islets from a cadaveric donorOrgan donation
Organ donation is the donation of biological tissue or an organ of the human body, from a living or dead person to a living recipient in need of a transplantation. Transplantable organs and tissues are removed in a surgical procedure following a determination, based on the donor's medical and...
pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
using a mixture of enzymes called Liberase (Roche). Each recipient receives islets from one to as many as three donors. The islets are infused into the patient's portal vein, and are then kept from being destroyed by the recipient's immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
through the use of two immunosuppressants, sirolimus
Sirolimus
Sirolimus , also known as rapamycin, is an immunosuppressant drug used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. A macrolide, sirolimus was first discovered as a product of the bacterium Streptomyces hygroscopicus in a soil sample from Easter...
and tacrolimus
Tacrolimus
Tacrolimus is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection...
as well as a monoclonal antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
drug used in transplant patients called daclizumab
Daclizumab
Daclizumab is a therapeutic humanized monoclonal antibody to the alpha subunit of the IL-2 receptor of T cells. It is used to prevent rejection in organ transplantation, especially in kidney transplants....
.
History
Islet isolation and transplantationOrgan transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
was pioneered by Paul Lacy throughout the 1960s. He and Walter Ballinger together were able to restore normoglycaemia in diabetic rat
Rat
Rats are various medium-sized, long-tailed rodents of the superfamily Muroidea. "True rats" are members of the genus Rattus, the most important of which to humans are the black rat, Rattus rattus, and the brown rat, Rattus norvegicus...
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
James Shapiro
James Shapiro, MD was born in Leeds, England and obtained his medical degree at the University of Newcastle upon Tyne. He is currently a Canadian Research Chair in transplantation and the Director of the Clinical Islet Transplant Program at the University of Alberta in Edmonton, Canada.Shapiro is...
(transplant surgeon), Jonathan Lakey Ph.D., Dr Edmond Ryan (endocrinologist
Endocrinology
Endocrinology is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions called hormones, the integration of developmental events such as proliferation, growth, and differentiation and the coordination of...
), 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 the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
in July 2000.
The NEJM report was exciting for the diabetes field because all seven patients undergoing the Edmonton Protocol remained insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
-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.
"Since 2000, Several hundred people have received islet transplants, by a year after transplant, 50 - 68% of patients do not need to receive additional insulin, but by five years after the procedure, few than 10% of total patients are free of daily insulin supplementaition."
Further reading
- 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.