Diabetes is a major health concern to today's modern society. Not only does its prevalence grow rapidly in many countries, but it is also the leading cause of death, blindness, amputation and kidney failures. Some scholars even dubbed diabetes as the “21st-century plague”.

While both type I and type II diabetes are equally debilitating, type I diabetes is generally thought of as more serious and warrant a more radical treatment approach. According to a 2010 report, people with type I diabetes are estimated to live 20 years shorter than healthy individuals. 

Gene therapy successfully cured diabetes in mice

Regular insulin injections are the only effective treatment for patients with type I diabetes. However, that may change as scientists have recently discovered that mice with type I diabetes could be successfully cured with gene therapy. 

The research team, led by Bruno Doiron and Ralph DeFronzo, used an innovative approach to solve the problem of insufficient insulin production by the pancreatic beta cells. They named their approach as CNIP, or “Cellular Networking, Integration and Processing”.

CNIP involves targeting multiple process levels of cellular physiology important in beta cell formation. Virus vectors were employed to transfer selected genes into the pancreas in order to induce beta cell formation in vivo in mice, directly from other pancreatic somatic cells.

“The pancreas has many other cell types besides beta cells, and our approach is to alter these cells so that they start to secrete insulin, but only in response to glucose,” said one of the lead authors, Ralph DeFronzo, professor of medicine and chief of the Division of Diabetes at the university.

The diabetic mice in the study were cured of the disease for one year without any side effects. 

Potential therapeutic approach in humans

With the success of the study, there stands a chance for patients to be entirely cured of diabetes, at least for type I. People don’t have symptoms of diabetes until they have lost at least 80% of their beta cells, said Doiron, who is an assistant professor of medicine at UT Health.

“We don’t need to replicate all of the insulin-making function of beta cells,” he said. “Only 20% restoration of this capacity is sufficient for a cure of type I.”

Although the exact causes of the disease still remain unknown, medical experts are fairly confident that in patients with type I diabetes, the body's immune system has mistakenly destroyed pancreatic beta cells that produce insulin. The rest of the pancreatic cell populations, however, are not damaged by the immune system and therefore could be genetically altered.

“If a type 1 diabetic has been living with these cells for 30, 40 or 50 years, and all we’re getting them to do is secrete insulin, we expect there to be no adverse immune response,” said DeFronzo.

The researchers also proclaimed that their therapy was capable of regulating blood glucose level precisely, at least in their mouse model, thereby circumventing the problem of hypoglycaemia. This represents a tremendous advantage over many other treatments, including oral hypoglycaemic medications and insulin.

Researchers expect human clinical trials in three years

It is important to remember, however, that results taken from lab animals can rarely be translated directly into clinical benefit. Mice are different from humans in many aspects after all.

“We cured mice for one year without any side effects. That's never been seen. But it's a mouse model, so caution is needed,” said Doiron. “We want to bring this to large animals that are closer to humans in physiology of the endocrine system.”

The study team hopes to reach human clinical trials in three years time. However, the road to marketing authorisation is not straightforward, but full of obstacles.

Nevertheless, should this technology obtain the necessary green light from the regulatory authorities, it will significantly reduce the burden of diabetes in most, if not all, countries suffering from this epidemic. MIMS

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https://clinical-and-molecular-endocrinology.imedpub.com/a-simply-way-to-generate-pancreatic-beta-cell-formation-in-vivo-through-cellular-networking-integration-and processing.pdf