Texas scientists closer to diabetes cure with unconventional approach


Highlights

Years of testing remain, but UT Health San Antonio researchers say they’ve cured Type 1 diabetes in mice.

In peer-reviewed paper, they say a “gene transfer” can “wake up” cells in the pancreas to produce insulin.

Health researchers at the University of Texas think they have found a way to trick the body into curing Type 1 diabetes.

The immune system of a person with diabetes kills off useful “beta” cells, but the UT researchers say they have found a way to make other cells in the pancreas perform the necessary work. Their approach, announced earlier this month in the academic journal Current Pharmaceutical Biotechnology, not only would have implications for Type 1, formerly called juvenile diabetes, but also could help treat the far more common Type 2 variety, also known as adult-onset diabetes.

The researchers have cured mice, which are genetically similar to people but different enough that new rounds of animal testing — and millions of dollars more — are needed before human trials can begin. The researchers’ approach is sure to garner skeptics, at least in part because it is a significant departure from the many other attempts at curing diabetes, which typically involve transplanting new cells and/or suppressing the immune system’s attempts to kill off useful ones.

By contrast, “we’re taking a cell that is already present in the body — it’s there, and it’s happy — and programming it to secrete insulin, without changing it otherwise,” said Ralph DeFronzo, chief of the diabetes research at the UT Health Science Center at San Antonio.

Diabetes is a disease characterized by a person’s inability to process carbohydrates, a condition that if untreated can lead to often-catastrophic health consequences: lethargy, diminished eyesight, heart attacks, strokes, blindness and a loss of circulation in the feet that could lead to amputation. The Centers for Disease Control and Prevention estimate that in 2014, about 29 million Americans – almost 1 in 10 – had diabetes.

The core problem is insulin. Most people naturally secrete that substance when they eat something with carbohydrates, such as bread, potatoes and candy bars. Insulin acts like a concierge that escorts the sugar from the bloodstream into the cells, providing the cells with the energy to function. In most people, the body is continually monitoring blood sugar and producing insulin as needed.

In Type 2 diabetes — which makes up 9 out of 10 diabetes cases and is generally associated with older people and weight gain — the cells reject the insulin, causing sugar to build up in the bloodstream even as cells are starved for energy. Type 2 is often treated with pills that tell the cells to let in the insulin. But in Type 2 diabetes, the body also often gradually loses the ability to produce insulin, requiring insulin injections.

In Type 1 — the type the researchers studied — the body has simply stopped producing insulin. This type often manifests in children, though it can sometimes develop in adults as well.

The reason the body stops producing insulin is that it kills off the pancreas’ beta cells, which produce insulin. People with Type 1 diabetes must get their insulin from injections or occasionally inhalation, a cumbersome and often imprecise task. Too little insulin and blood sugar levels stay high for extended periods, potentially damaging the body; too much and blood sugar levels crash, possibly causing a person with diabetes to faint or experience an even worse problems, such as a stroke.

DeFronzo’s partner, Bruno Doiron, decided to see whether the body could reliably produce insulin without transplanting new cells. He used a “gene transfer” technique on mice, delivered via a virus, that activated insulin production in cells already in the pancreas — for instance, those that produced certain enzymes.

“We’re not fundamentally changing the cell,” DeFronzo said. “We’re just giving it one additional task.”

The mice immune systems did not attack the new insulin-producing cells. Most important, according to the findings: The cells produced the right amount of insulin: not so much that they sent a mouse into a blood sugar free fall, not so little that blood sugar levels stayed high. The mice have shown no sign of diabetes for more than a year, according to the findings.

Quite a bit of work remains before testing will start on people. If they can raise enough money — they estimate $5 million to $10 million — they can proceed to testing on larger animals, such as pigs, dogs or primates, a next step that would be planned in conjunction with the U.S. Food and Drug Administration.

They hope to start human trials in three years.

DeFronzo and Doiron said they expect skepticism but said much of it will be driven by how unconventional their work is. Doiron added that, although the technique is unconventional in the context of diabetes, using a virus to deliver a gene transfer is an established technique, having been approved dozens of times by the FDA to treat diseases.

“We can use the cells the body has naturally,” Doiron said. “This will simply wake up the cells to produce insulin.”



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