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Health & Medicine Newly Discovered Hormone Could Become Wonder Drug Against Diabetes

Newly Discovered Hormone Could Become Wonder Drug Against Diabetes

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First Posted: Apr 29, 2013 02:01 AM EDT

A major research breakthrough was achieved in the field of diabetes by scientists at the Harvard Stem Cell Institute (HSCI) who discovered a hormone that could soon enable a dramatically more effective treatment of type 2 diabetes.

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A hormone called betatrophin was surprisingly found to cause mice producing insulin-secreting pancreatic beta cells at up to 30 times the normal rate. The new beta cells only produce insulin when called for by the body, offering the potential for the natural regulation of insulin and a great reduction in the complications associated with diabetes.

The astonishing results of HSCI co-director Doug Melton and postdoctoral fellow Peng Yi, published in the journal Cell and supported in large part by a federal research grant, already attracted the attention of drug manufacturers which could lead to speedy clinical trials.

"If this could be used in people," said Melton, a Harvard professor and co-chair of the University's Department of Stem Cell and Regenerative Biology, "it could eventually mean that instead of taking insulin injections three times a day, you might take an injection of this hormone once a week or once a month, or in the best case maybe even once a year."

 

Diabetes
(Photo : Flickr.com/Jose Gulao)

Type 2 diabetes is a disease where patients slowly lose beta cells and the ability to produce adequate insulin due to a combination of overweight and lack of exercise. One recent study has estimated that diabetes treatment and complications -- just one element of the national obesity epidemy -- cost the United States $218 billion annually, or about 10 percent of the nation's entire health bill.

 

"Our idea here is relatively simple," Melton said. "We would provide this hormone, the type 2 diabetic will make more of their own insulin-producing cells, and this will slow down, if not stop, the progression of their diabetes. I've never seen any treatment that causes such an enormous leap in beta cell replication."

The scientist hopes that the hormone could also play a role in treating juvenile diabetes type 1, the disease that afflicted two of his children and that he originally focused on for that reason -- for 15 years now.

"We've done the work in mice," Melton said, "but of course we're not interested in curing mice of diabetes, and we now know the gene is a human gene. We've cloned the human gene and, moreover, we know that the hormone exists in human plasma; betatrophin definitely exists in humans."

While more research is needed before the hormone could be available as a drug, Melton stated he hopes that betatrophin could be in human clinical trials within three to five years, which would be a very short time in the normal course of drug discovery and development.

Working with Harvard's Office of Technology Development, Melton and Yi already established a collaborative agreement with Evotec, a German biotech firm that now has 15 scientists working on betatrophin, and the compound has been licensed to Janssen Pharmaceuticals, a Johnson & Johnson company that now, too, has scientists working to move betatrophin toward the clinic.

The discovery of betatrophin is also an important example why federal funding of basic science research is absolutely crucial, as it is the result of open-ended research without any guarantee for results. According to Melton, his proposal was titled "Searching for Genes and Compounds That Cause Beta Cell Replication", which convinced National Institutes of Health grant reviewers, receiving federal funding for 80 percent of the work leading to the discovery of betatrophin.

"At a time of great uncertainty for federal research funding, the discovery of betatrophin is a reminder of the importance of basic research," stated Harvard Provost Alan Garber. "Were it not for a National Institutes for Health grant, this promising new approach to treating diabetes might never have come to light."

As is often the case in basic science research, serendipity played a role in the discovery of betatrophin:

For more than 15 years the major focus of Melton's work has been not type 2 diabetes but the less common type 1, or juvenile diabetes, which he began focusing on when his son was diagnosed with it as an infant. (The disease later was also diagnosed in his daughter.) Additionally, most of Melton's work has involved using stem cells, the fundamental building blocks of all human organs, as disease treatments and targets for drug discoveries. But stem cells played no direct role in the discovery of betatrophin. It was, rather, a classic example of scientists with sufficient resources asking questions, and pursuing answers, that fell outside the usual scope of their laboratories and institutes.

 

Paper:

Peng Yi, Ji-Sun Park, Douglas A. Melton, Betatrophin: A Hormone that Controls Pancreatic β Cell Proliferation, Cell, 2013, DOI: 10.1016/j.cell.2013.04.008

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