Game Changing Diabetes Breakthrough in 2014?

Richard (Rick) Mills
Ahead of the Herd

 page 1 of 3

 

As a general rule, the most successful man in life is the man who has the best information

 

In a person with diabetes, the insulin producing beta cells in the pancreas are attacked by the immune system and destroyed, this leads to a deficiency of insulin and high blood sugar (glucose).

 

People with insulin-dependent diabetes (all of type-1 and about 27 percent of type-2 diabetics) lack the necessary amount of insulin in their bloodstreams. This can, and often does lead to irreversible damage to their hearts, blood vessels, eyes, kidneys, skin, feet and hearing.

 

Diabetes is not considered a high mortality condition, but it is a major risk factor for other causes of death and has an extremely high attributable burden of disability, for example; two percent of people with diabetes become blind and roughly ten percent develop severe visual impairment, fifty percent of people with diabetes die of cardiovascular disease.

 

There is no cure for diabetes. The Standard of Care for patients with reduced or missing critical hormones or proteins, such as insulin, is often monitoring and injecting these proteins multiple times a day.

 

Edmonton Protocol

 

Paul Lacey was a researcher at Washington University when, in 1972, he cured/restored normoglycaemia in some diabetic rats by transplanting islet cells (clusters of thousands of endocrine cells that include beta cells that produce insulin) from healthy rats into the livers of some diabetic rodents.

 

Over the next two decades researchers made hundreds and hundreds of attempts to apply the procedure to humans. Unfortunately no one was successful. By the early 1990’s most scientists had come to the conclusion that islet-cell transplantation was a lost cause.

 

Dr. James Shapiro, Dr. Jonathan Lakey and colleagues from the University of Alberta in Edmonton developed the Edmonton Protocol in the late 1990s.

 

The Edmonton Protocol is a method of implantation of pancreatic islets into the portal vein  (a large vein returning blood from the abdomen to the liver), of the recipient’s liver.

 

The first patient was treated in March of 1999. The protocol was published in the New England Journal of Medicine in July 2000. Considerable excitement was created by the report – the first seven patients were still insulin-independent after an average of 12 months.

 

How it works

 

Researchers use specialized enzymes to remove islets from the pancreases of recently deceased adults. The islets are then purified and counted.

 

Each transplant patient receives islets from one to three donors. X rays and ultrasound guide the placement of a thin, flexible tube called a catheter through a small incision in the upper abdomen and into the portal vein. The islets are then infused – pushed – slowly into the liver through the catheter.

 

The islets are kept from being destroyed by the recipient’s immune system through the use of two immunosuppressant drugs as well as an antibody drug specifically used in transplant patients.

 

Once implanted, the beta cells in the transplanted islets begin to make and release insulin. However full islet function and new blood vessel growth from the new islets takes time so transplant recipients usually need to take insulin injections until the islets are fully functional.

 

Since 2000 several hundred people have received islet transplants – but by five years after the procedure, fewer than 10 percent of all patients are free of daily insulin supplementation.

 

Obstacles to Edmonton Protocol

 

The shortage of islets is a significant obstacle, organ donor rates are generally very low and especially so in Canada. Unfortunately, many of the pancreases that are donated are not suitable for extracting islets because they do not meet the selection criteria and islets are often damaged or destroyed during processing. The number of islet transplants that can be performed each year is therefore limited by a severe shortage of suitable islets.

 

Immunosuppressive medications have significant side effects and long-term effects are still not fully known. Immediate side effects may include mouth sores and gastrointestinal problems – an upset stomach and diarrhea.

 

Patients may also suffer from:

• Increased blood cholesterol, or blood fat, levels
• High blood pressure
• Anemia
• Fatigue
• Decreased white blood cell counts
• Decreased kidney function
• Increased susceptibility to bacterial and viral infections
• Increased risk of developing certain tumors and cancers

Unfortunately  the autoimmune response that destroyed the transplant recipients’ own beta cells in the first place can happen again.

 

There are issues with infusion of islets into the portal vein, an immediate blood mediated inflammatory reaction (IBMIR) causes over 50 percent of islets to die within hours or days following infusion into the blood.

 

Another issue is that the liver site is associated with islet transplant related procedural complications including catheter-induced hemorrhage and thrombosis. Additional inhibiting factors include difficulty in imaging the islets, an inability to remove the transplanted islets and the limited number of islet transplants a patient can receive.

 

The State of Islet Transplantation today

 

From the report ‘Improvement in Outcomes of Clinical Islet Transplantation: 1999–2010’  the author found on diabetesjournals.org comes the following…

“Allogeneic islet transplantation offers a minimally invasive option for β-cell replacement in people with type 1 diabetes complicated by recurrent severe hypoglycemia and/or marked glycemic lability.

 

Before 1999, less than 10% of islet transplant recipients achieved insulin independence. In 2000, the Edmonton Protocol for islet transplantation achieved insulin independence in seven consecutive participants who received islets from more than one donor under a steroid-free immunosuppression regimen. After this proof-of-concept success, islet transplant programs expanded in North America and elsewhere. These centers have offered evolving strategies of islet preparation and immunosuppression, although the limited resources available have prevented anything but independent Phase I/II attempts to standardize processes, achieve success, and stabilize outcomes.

 

Even in the absence of insulin independence, an islet transplant can protect type 1 diabetic recipients from severe hypoglycemic episodes as long as residual islet graft function is maintained, as proven by restoration of C-peptide production. Despite this compelling rationale, islet transplantation for type 1 diabetes has produced variable success and elusive durability, has frequently required multiple donor organs, and has balanced one disease load – severe hypoglycemia – with another – long-term immunosuppression.”

A search has been on for an alternative site for islet transplantation as well as for an optimal medical device in which to implant the islets. Several subcutaneous devices have previously been developed for islet transplantation but from a preclinical and clinical perspective the results from these products have been generally disappointing.

 

Current cell therapy is limited to poor cell survival, inappropriate delivery of hormones, a lack of available donors and cells.

 

 

1|

2|

3|

Next»