Disarmed Virus Takes Shot at Diabetes Cure

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A team of researchers at Baylor College of Medicine has discovered that stem cells already existing in the body are key players behind a gene-therapy regimen that appears to permanently cure Type 1 diabetes in mice.

According to the Centers for Disease Control and Prevention, Type 1 diabetes, a condition where the body does not produce enough insulin to maintain healthy sugar levels in the blood, accounts for between 5 and 10 percent of the nearly 36 million cases of adult diabetes in the United States.

People living with the Type 1 diabetes are tied to a life of daily glucose monitoring and insulin injections, but research recently published in the journal Developmental Cell gives hope to these patients that this cumbersome daily routine could one day be a thing of the past.

The researchers induced diabetes in mice by injecting them with streptozotocin, a chemical that destroys the pancreatic “islet” cells that produce insulin in both mice and human bodies.

The newly diabetic mice were injected with a “disarmed” virus (one that does not induce negative health effects) containing the protein called Neurogenin3. The protein, also called Ngn3, is only expressed during embryonic development in healthy, non-diabetic mice and is associated with the creation of insulin-producing pancreatic islet cells.

Following the virus injection, the adult mice had regular, healthy blood-glucose levels for the rest of their lives.

By analyzing post-mortem livers of their test subjects, the scientists observed that when Ngn3 is first introduced to the rat’s body, it induces normal, mature liver cells to produce insulin. However, the effect on these cells is temporary, and their ability to produce insulin is lost after six weeks.

Before these liver cells stop producing insulin, stem cells residing elsewhere in the liver convert into islet cells. Similar in appearance to normal pancreatic islet cells, these “new” islet cells were responsible for producing enough insulin to reverse diabetes in the mice.

“The most important aspect of our finding is the proof of concept that we can turn adult stem cells in the liver into pancreatic islets,” says lead researcher Lawrence Chan. ”(Now) that we know these adult stem cells are the key to the response, we can direct future experiments.”

So will future experiments be applied to humans?

That first depends on whether a suitable disarmed virus can be found to deliver Ngn3 to human livers, Chan said. “I suspect that if you can deliver Ngn3 with a (virus) that is nontoxic to humans — a big if — there is a good chance you can turn (human) adult stem cells in the liver into islets.”

He also cautions that their results cannot automatically be applied to humans because most cases of Type 1 diabetes in humans are not caused by streptozotocin injections but by an autoimmune disorder where the body’s immune system destroys islet cells.

“If we were to try the same Ngn3 treatment in autoimmune type 1 diabetic mice, the newly formed islets that appear after the treatment will be destroyed right away (and) we fail to cure diabetes,” Chan said. “However, (we) are developing a strategy to engineer a protective shield for the newly formed islets that will enable them to survive the onslaught of autoimmunity. A combination treatment has succeeded in reversing the diabetes in our pilot experiments (and we) expect exciting developments in the coming months.”

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