Science in the Triangle

INTRODUCTION

Tranzyme Pharma is one of dozens of drug development companies in North Carolina’s Research Triangle area, a biotech hot spot that is ranked third in the nation by number of companies. The Durham company has diligently advanced therapies based on a hormone that was discovered a decade ago, a technology also used by two rivals. Now, Tranzyme’s Board of Directors has to decide how to pay for the final development step and get its drugs to market: Go public, sell the company or go back to its investors hat in hand one more time.

This is the first part of three.

People who claim their weight problem is related to a gland aren’t all wrong.

Sure, taking in too many calories and not exercising enough carry much of the blame for the obesity epidemic. But there is indeed a gland that plays a role in feeling hungry.

It’s the pituitary gland, an important structure that sits at the base of the brain and is about the size and shape of a garbanzo bean (shown in picture).

A hormone produced mostly in the stomach lining provides a key signal that it’s time to eat. Discovered by Japanese researchers in 1999, ghrelin gets around in the blood. It can be found in many places in the body, including the brain, the heart and the digestive tract.

Ghrelin stimulates the release of growth hormones in the pituitary gland. Researchers believe that this partly explains why teen-age boys can have such outsized appetites.

There’s a lot that researchers have yet to figure out about ghrelin, for example how it affects insulin producing cells in the pancreas as food is digested into glucose. Generally, high ghrelin levels are linked to low levels of insulin.

Insulin is a hormone that helps cells absorb glucose from the blood as fuel. Blood glucose levels rise when cells have a harder and harder time responding to insulin or when the pancreas produces insufficient amounts of insulin. The result is frequently Type 2 diabetes, a disease linked to obesity and other risk factors.

In 2007, an estimated 24 million Americans, or 7.8 percent of the U.S. population, suffered from Type 2 diabetes, according to the National Diabetes Information Clearinghouse, which is part of the National Institutes of Health.

The disease is particulalry prevalent among Americans 60 years and older. (See NDIC chart.)

The discovery of ghrelin, which was published December 1999 in the science journal Nature, was a breakthrough.

It wasn’t easy to find and synthesize it, Masayasu Kojima, one of the researchers who discovered it, wrote in the journal ScienceDirect.

The hormone’s chemical structure and its origin in the stomach surprised the researchers. Its existence had long been suspected, because ghrelin receptors, places in a cell where it docks, were known. But the Japanese researchers had expected ghrelin to be produced in the brain. The discovery took more than a year and one failed test after another, Kojima wrote.

The day the correct synthesized sample was ready, Kojima bicycled to pick it up.

“On my way back I espied a bale of turtles swimming in the Senri river,” he wrote. “This brought me high hopes for the sample: for the turtle is respected as an augury of good fortune in Japan.”

The tireless work of the Japanese researchers revealed the origin and the structure of ghrelin. Their discovery allowed chemists at pharmaceutical companies to come up with versions of the hormone that target particular areas in the body.

Three East Coast companies were inspired to develop ghrelin therapies. One of them is Tranzyme Pharma, a drug development company in Durham, just south of Research Triangle Park.

Each company is using a different version of ghrelin and is testing them in animals or patients.

It is unclear which version will make it all the way to the pharmacy shelve. Much work remains to be done, said Mark Peterson, an organic chemist who is Transzyme’s vice president of operations. “People know a lot about ghrelin and ghrelin receptors,” Peterson said. “But there is still a lot to be learned about the molecular biology.”

Continued in part 2.