By Lisa Collier Cool
A potential cure for diabetes may be one step closer to reality, report scientists in an article published yesterday in the online issue of the journal Natural Communications.
By turning off a single gene, researchers at Columbia University Medical Centre (CUMC) have transformed human gastrointestinal cells into insulin-producing cells. Their work offers hope to patients with type 1 diabetes, who currently rely on insulin injections to regulate their blood sugar.
“What we’re aiming to do, in the best case scenario, is cure the disease,” explains the study’s senior author, Domenico Accili, MD, the Russell Berrie Foundation Professor of Diabetes at CUMC.
“We hope to develop a drug—ideally a pill—that patients would take maybe once a month, instead of multiple insulin injections daily, to control their blood sugar. That would be the blue-sky scenario. But there are intermediary outcomes that would also be desirable. For example, maybe we could have a drug that would let people inject insulin only once a day or stop taking insulin at night.”
Breakthrough follows decades of research
For almost two decades, scientists have tried to create insulin-producing cells to replace those lost in type 1 diabetes.
Insulin is a hormone that helps the body regulate metabolism and remove excess glucose from the bloodstream. It is usually produced by cells in the pancreas. But in people with type 1 diabetes, insulin-producing cells are destroyed by the immune system.
In previous research, investigators have used stem cells to create insulin-producing cells in the lab. Unfortunately, those surrogate cells have not responded appropriately to glucose. If they were introduced to a human body, they would release insulin even when it wasn’t needed—which could lead to dangerously low blood sugar.
In contrast, the Columbia University researchers have retrained human intestinal cells to release insulin in response to glucose. Their findings suggest it may be easier to reeducate existing cells in patients with diabetes, rather than transplant new cells created in a lab.
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Researchers modified intestinal cells grown in lab
First, Dr. Accili and postdoctoral fellow Ryotaro Bouchi created a tissue model of the human intestine using pluripotent stem cells from healthy human donors. Then the researchers applied genetic engineering to deactivate the gene FOXO1 in the intestinal cells.
After seven days, some of the retrained intestinal cells began to produce insulin. Best of all, they released the insulin in response to glucose—like natural insulin-producing cells.
This work draws on previous research in mice conducted by Dr. Accili and colleagues, who found that insulin produced by modified gut cells helped to normalized blood sugar in otherwise diabetic mice.
Retrained cells may be more resilient
It’s possible that insulin-producing intestinal cells may be destroyed by the immune system in patients with type 1 diabetes. However, Dr. Accili suspects that retrained intestinal cells may be more resilient than natural insulin-producing cells.
“In the pancreas, insulin-producing cells form very slowly,” he explains. “So they are sitting ducks for the immune system and very easy to kill. In contrast, cells in the intestine turn over very quickly, every seven to ten days. It would be practically harder for the immune system to take them out in such a short period of time.”
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Ongoing research needed to develop trial drug
These breakthrough findings offer hope to patients with type 1 diabetes and the doctors who treat them—but the new line of gene therapy isn’t ready for the mainstream yet.
Before it can be applied to human patients, researchers need to identify a drug that could be used to deactivate gene FOXO1. Then they have to test the drug through clinical trials.
“I suspect it will be 18 to 24 months before we’re ready to declare whether we have a drug candidate for trial,” says Dr. Accili. “Then from the time that a clinical trial starts to when the drug is proved and ready for use, it could be three years, it could five years, it could be ten.”
“We’re very committed to this area of work,” he adds. “We’ll continue to work as fast as we can with the resources available to us. But we also want to develop a treatment that is safe and effective as possible.
