Studies of growth hormone result in new class of drugs

October 31, 1999

ATHENS, Ohio--Studies at Ohio University of growth hormone and its role in diabetes, acromegaly, cancer and other health problems have resulted in the discovery of protein antagonists that have been used to develop a new class of drugs for the treatment of these and other diseases.

Ohio University recently received the third U.S. patent in a series on the technology, growth hormone antagonists, which is the basis for the development of the drug termed pegvisomant. This summer, scientists in Texas announced the positive results of Phase III clinical trials of pegvisomant for the treatment of acromegaly, a disease that affects about 40,000 people worldwide. Sensus Drug Development Corp., the company that developed pegvisomant, plans to file for Federal Drug Administration approval for the drug's use in acromegaly early next year.

"Not many university professors are able to see something discovered in their laboratory be used successfully in the treatment of a human disorder. We are very proud of our discovery of this new class of drugs," said John Kopchick, Goll-Ohio Eminent Scholar and professor of molecular and cellular biology at Ohio University. "We've discovered something that can be used to treat human illness and save lives."

Kopchick and former Ohio University scientist Wen Chen discovered growth hormone antagonists just 10 years ago in labs in the university's Edison Biotechnology Institute, where Kopchick is a senior scientist. Human and animal growth hormones contain a chain of 191 amino acids. Kopchick's research team discovered that by replacing the amino acid glycine -- number 119 in the chain in animals and 120 in humans -- with almost any other amino acid, the growth hormone turns from a growth hormone agonist, or enhancer, to a growth hormone antagonist, or inhibitor.

The antagonist inhibits the action of the hormone at the cellular level by competing for receptors usually claimed by growth hormone, thus inhibiting the biological activity of the hormone.

Animal studies at EBI of the antagonists' effect on acromegaly were successful, laying the groundwork for the human trials that concluded earlier this year.

"Our antagonists inhibit growth hormone activity in scenarios where excessive growth hormone action may be implicated in a disease," said Kopchick, who added that his work and studies elsewhere suggest growth hormone is involved in the progression of diabetic kidney disease and breast cancer. His research team now is conducting animal studies of the growth hormone antagonists' ability to halt the progression of diabetic nephropathy and breast cancer.

Growth hormone's role in these diseases was not as obvious as the hormone's role in acromegaly, which is caused by a brain tumor that causes the pituitary gland to produce massive amounts of growth hormone. The disease, most commonly seen in middle-aged adults, is characterized by abnormal growth of the hands, feet, and bone and cartilage in the face and other parts of the body; and enlargement of the liver, spleen, kidneys and heart.

Earlier this year, scientists with Sensus, which holds the license for the growth hormone antagonist technology, announced the results of Phase III clinical trials of the growth hormone antagonist drug pegvisomant. The trials were conducted at 16 medical centers in the United States and Europe with 111 patients. Patients in the active treatment groups received 10, 15 or 20 milligrams per day for 12 weeks. According to findings presented at the Endocrine Society's annual meeting in June, pegvisomant was well-tolerated and no major adverse events were reported throughout the course of the study. Pegvisomant has been granted "fast track" review by the FDA.

The latest patent issued to Ohio University and Kopchick for growth hormone antagonists deals with the use of growth hormone antagonist for the treatment of many diseases, including acromegaly. The university also recently received notice that a European patent will be issued on the technology before the end of the year. The university received U.S. patents on growth hormone antagonists in 1994 and 1997.
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The Edison Biotechnology Institute is a biomedical genetics institute at Ohio University and part of the Ohio Department of Development's Thomas Edison Program. Kopchick, who holds a faculty appointment in the College of Osteopathic Medicine, is a recipient of the state of Ohio's Eminent Scholar Awards.

Written by Kelli Whitlock.

Contact: John Kopchick, Edison Biotechnology Institute, (740) 593-4534, kopchick@ohio.edu ; Gary Meyer, Technology Transfer Office, (740) 593-1818, meyerg@ohio.edu

Ohio University

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