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Wednesday, August 28, 2019

Transplanting islet cells can fix brittle diabetes. Why not do this in the U.S.?

The term “type 1 diabetes” generally conjures up images of insulin. That makes sense, because insulin is the main treatment for this common disease. But it isn’t a cure. A type of cell transplant that comes close to a cure for some people with type 1 diabetes, a technique pioneered and tested in the United States, is now available in many countries but is still deemed an experimental procedure in the U.S., making it almost impossible to get.
That doesn’t make sense to us.
Type 1 diabetes, which affects 1.25 million American children and adults, and more than 20 million people around the world, is a challenging chronic disease caused by the body’s inability to make insulin. Among its most severe forms is brittle diabetes. People with brittle diabetes frequently experience large swings in blood sugar that can quickly move from too high to too low or vice versa. Severely low blood sugar, called hypoglycemia, can cause sudden and unexpected seizures, coma, heart attacks, and even death.
Insulin is made by specialized cells in the pancreas called islet cells. Transplanting these cells from a donated pancreas to an individual with brittle diabetes can restore the recipient’s ability to naturally produce insulin. The procedure has a record of effectiveness. A Phase 3 clinical trial sponsored by the National Institutes of Health, for which one of us (C.R.) was an investigator, showed that such transplants worked in 80% to 90% of the patients treated in eight centers in North America. The procedure virtually eliminated the risk of life-threatening hypoglycemia one and two years after the transplant. As with other types of transplant, the recipient must take anti-rejection drugs.
Individuals with brittle diabetes in Canada, Europe, Asia, and Australia can receive islet cell transplants, much the same way that individuals who need new hearts or livers can receive transplants. Islet cell transplants are even performed in China and Iran, whose doctors came to the U.S. to learn the technique and carried it back home. So why is this successful procedure, which can vastly improve the lives of those living with brittle diabetes, available in the U.S. only after a convoluted process that is often impossible to complete?
If a patient needed a pancreas transplant (which would include islet cells), he or she would be registered on the national organ transplant list and, once a pancreas became available, would receive the transplant, which is generally paid for by insurance.
But for a less-invasive islet cell transplant, an institution that wants to perform the procedure must file an investigational new drug application with the Food and Drug Administration, a very challenging process — and also figure out how to pay for the transplant.
That’s due to the way the FDA interprets the code of federal regulations; specifically the criteria of minimal manipulation of human cells, tissues, and cellular and tissue-based products.
After islet cells are extracted from a donated pancreas, they need to sit in a culture medium at a temperature between 72 and 75 degrees Fahrenheit for two to three days. This gives the transplant team time to perform quality controls on the cells, and also to prepare the recipient for the transplant.
The FDA has interpreted the brief hiatus for islet cells as going beyond minimal manipulation, a concept based on the premise that processing cells does not alter their relevant biological characteristics. The hibernation process for islet cells does not change the cells’ characteristics or increase their number, both of which occur with the manipulation of advanced stem cell therapies, which reasonably need extra scrutiny.
The European Medicines Agency has determined that transplanting pancreatic islet cells should just follow the standard rules of organ transplantation, even though the cells require a brief hibernation period. This recommendation is based in part on its view that transplanting a pancreas, with islet cells intact, is an organ transplant, so there is no reason to treat transplantation of just the islet cells as anything different.
Because of the benefits to the thousands of Americans with brittle diabetes, there is a strong incentive to harmonize the FDA’s approach to islet cell transplantation with the EMA’s approach.
More than a decade ago, the United Kingdom’s National Health Service approved islet cell transplantation for type 1 diabetes — an approval based on an extensive review of the evidence generated by clinical trials conducted in the United States. Our federal dollars supported that research, and this treatment ought to be available to U.S. citizens.
Islet cell transplantation is not a panacea for all forms of type 1 diabetes. And transplantation of any organ, including islet cells, requires the use of anti-rejection drugs that can have a range of adverse side effects. That said, individuals with severe brittle diabetes who are fully informed of the risks and benefits should have the ability to access this lifesaving treatment option.
We fully understand the FDA’s efforts to rein in companies marketing unapproved stem cell products that have little or no evidence to support their use and that may put patients at risk. Yet the FDA should stay equally focused on its commitment to approving evidence-based transformative treatments for devastating diseases and conditions, including brittle diabetes.
Camillo Ricordi, M.D., is professor of surgery and medicine and chief of the Division of Cellular Transplantation at the University of Miami Miller School of Medicine, where he has directed the Diabetes Research Institute and Cell Transplant Center since 1996. Anthony Japour, M.D., is a medical director at ICON plc. The views expressed are those of the authors and not those of the University of Miami or ICON.

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