Diabetes Cure Research: Turning Duct Cells into Beta Cells

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As the parent of a child with type 1 diabetes, I avidly follow news about advances in treatment of the disease. As I’ve written, Bisi loves her new Omnipod pump; I have heard great things about the new Dexcom G4 Platinum CGM and suspect that Bisi will start using it in the not too distant future. I am excited about the potential of a closed-loop system that would presumably take much of the meal-to-meal management out of type 1 diabetes while also protecting against scary lows and highs. But none of this is enough. What I’m really interested in for my seven-year-old daughter is a cure.

When Bisi was diagnosed, several people tried to encourage us by saying how fast research is moving on the disease. Maybe, in a decade or so, the problem will be solved, they told us.  But I’m someone who was born the year Nixon declared war on cancer and I’ve since lost my aunt and then my father to that disease, so I’m skeptical whenever I hear talk of cures, especially for a problem as complicated as type 1 diabetes. Doug Melton, the co-director of the Harvard Stem Cell Institute who devoted his career to curing type 1 diabetes after both his children were diagnosed with it, told me before a recent talk he gave that type 1 diabetes is a much thornier problem to solve than cancer. The current funding landscape for type 1 diabetes makes it even less likely that a cure will be discovered anytime soon. According to the Juvenile Diabetes Cure Alliance, of the $400 million given to the JDRF, the American Diabetes Association, the Joslin Diabetes Center, and the Diabetes Research Institute Foundation last year, only 2% “went toward a cure that can be achieved by 2025; the rest went toward cures 100 or more years away, prevention research and other expenses.”

Susan Bonner-Weir
Susan Bonner-Weir

Susan Bonner-Weir, a senior investigator at the Joslin Diabetes Center, is one of those researchers looking for a cure, though her research looks only at the beta cell aspect of the type 1 diabetes conundrum. Any potential cure for type 1 diabetes will have to solve two large problems.  How do you regenerate an adequate supply of insulin-producing beta cells? And how do you turn off the autoimmune attack that characterizes type 1 diabetes? Bonner-Weir is concentrating on the first of these questions.

Earlier this year, Bonner-Weir  gave a talk at a Joslin symposium on cutting-edge research into type 1 diabetes. She began her talk with a quote from an early study of diabetes, written less than two decades after insulin was discovered.  “The pancreas in diabetes is not simply the scarred field of an old battleground, but is the actual field of conflict. It does not submit without a struggle to injury, but endeavors to regenerate.” Can this effort be exploited? Bonner-Weir asks.

Based partly on Joslin’s ongoing 50-year medalist study, in which every pancreas examined so far has still had scattered beta cells (despite at least five decades of diabetes), Bonner-Weir and other scientists have argued that either the beta cells in the pancreas continue to make copies of themselves, or that the pancreatic ducts, through a process called budding or neurogenesis, continue producing new cells. Bonner-Weir’s work focuses on this latter process, which she believes holds more hope for creating an adequate supply of beta cells.  (This hypothesis is backed up by studies of gastric bypass patients, who have been shown to regenerate beta cells after surgery not through replication of existing cells but through enhanced neurogenesis from the ductal cells.) “If you’re a type 1 patient, who has lost most of your insulin producing cells, you’re not going to be able to really expand by replication of those cells, because you have very few cells. But what I and others have suggested is that the duct population of the pancreas remains sort of a pool of potential progenitors,” Bonner-Weir explains. “Someone with type 1 still has many duct cells—they’re not the ones that are destroyed by the autoimmune attack,” she continues.

Right now, Bonner-Weir is trying to understand exactly how the progenitor cells change into beta cells, and how those cells then function. Once she understands that process, she explains, “We can take these cells and expand them massively so you could actually have enough cells to give back to a person.” 

Even if Bonner-Weir’s lab is able to figure out how to grow the duct cells into mature beta cells, these new cells would then face sustained autoimmune attack. Researchers, including Bonner-Weir’s husband, Gordon C. Weir, are looking into ways to protect beta cells through protective capsules made of algenate—a form of seaweed—or some sort of polymer.

Much work remains to be done. Yet Bonner-Weir is optimistic about the promise of duct cells as a home-grown factory for new beta cells. “You can actually see the straight line between, Yes, if you knew how this cell became a beta cell you could see how possibly you could get a therapy for humans.”

A researcher looking to solve even just one aspect of type 1 diabetes needs to have tremendous patience. Bonner-Weir has been investigating the question of how to produce new beta cells for years, and first published a study showing the promise of pancreatic ducts for producing new islet tissue almost 15 years ago. A parent hoping for a cure for this disease needs tremendous patience too. Yet work like this gives me hope that someday, maybe when my daughter is a parent herself, type 1 diabetes will no longer be something she needs to contend with every meal, every day.

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ronnie
ronnie

it would be awesome if that really happens

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