January 7, 2002
Research: Other Research
Question from Haledon, New Jersey, USA:
I was watching that crazy guy on the animal planet television show one night and he said something very briefly about the venom of the gila dragon being used to treat diabetes, but also said the venom is poisonous. Do you have any further information regarding this?
It’s true, and it’s a great story, one that I have been gathering interviews and notes on for five or six years now. I would like to write up some day, when and if the FDA approves the drug.
The story starts in a V.A. hospital in the Bronx in the 1980s. A doctor there named John Eng, who works with diabetes, was going through databases of compounds and noticed that this compound has a molecular end on it that would allow it to get through the blood-brain barrier. Then when he looked at its structure he noticed that about 50% of structure was homologous with GLP-1, which is a very interesting drug because it has a number of potentially useful actions, but the actions of GLP-1 are very short lived.
The compound that Dr. Eng discovered has some unique characteristics that are similar to GLP-1 which, for type 2 diabetes, can be very useful because it stimulates the secretion of insulin but does so only when glucose levels are high so it is self-regulating. It also doesn’t cause a weight gain and, in fact, somewhat reduces your appetite. His key paper was published in the Journal of Biological Chemistry, 1990, pages 20259-20262. The title is “Purification and structure of exendin-3, a new pancreatic secretory factor isolated from Heloderma horridum venom.”
Dr. Eng approached his employer, the V.A., and explained the situation, but they apparently they had no interest in helping him with his discovery, didn’t think it would go anywhere, and released all patent rights to him personally. However, Dr. Eng never gave up on his discovery.
At the American Diabetes Association meetings in San Francisco in 1996, he showed how this drug lowered glucose even better than GLP-1, plus it lasted longer. He was able to modify exendin-3 and exendin-4 to have it last up to 24 hours. What Dr. Eng discovered is now called exendin-4 (AC2993), because it is a 39-amino acid peptide.
A start-up pharmaceutical company in San Diego, California, named Amylin Pharmaceuticals, Inc., was impressed and immediately snapped up the rights to his discovery. Exendin is one of the components of gila monster venom. The gila monster is one of only two poisonous lizards in the world. It is found in Arizona and the other is the beaded lizard of Mexico. In fact, Amylin bought the rights to use exendin produced by both of those animals. Nevertheless, they don’t have any gila monsters in their laboratories so they make Exendin synthetically. It won’t poison you. and the company says that AC2993 is currently in Phase 2 evaluation for the treatment of type 2 diabetes. So, there are still several years to go before the drug can come to market, if it ever does. The main problem with it now is that it needs to be taken by a daily injection, but the company is working on monthly injection and alternative delivery means.
Additional comments from Dr. Linda DiMeglio:
There are studies going on a novel drug known now just as “AC2993” – being investigated by Amylin Pharmaceuticals. AC2993 is a synthetic version of exendin-4, a peptide isolated from the salivary secretions of the Gila monster – a hormone with close homology to and a longer duration of action than the human glucagon-like peptide (GLP-1). It may work as a drug for type 2 diabetes and related metabolic disorders. It works by stimulating insulin secretion if blood sugars are high and slowing stomach emptying. Currently the drug does not have FDA approval in the US.