Thought I would post this here even though it's about a substance that's not actually Gila venom...
THE WALL STREET JOURNAL
Tuesday, June 17, 2003
GILA MONSTER DROOL CUTS APPETITE
Hormone in Lizard Saliva Leads to Drug that Curbs Diabetes and Overeating
By Marilyn Chase
NEW ORLEANS -- Could injecting an ingredient in Gila monster saliva spell salvation for some people with Type 2 diabetes? That is the hope of researches investigating one of a new class of substances known collectively as gut hormones.
Gut hormones are chemical signals passed between the gut and brain that control things like appetite and eating, energy use or fat storage, and the all-important satiety signal that tells people they have eaten enough, and it is time to push back from the table. More than two dozen such substances are being investigated in many academic and corporate labs, according to scientists at the American Diabetes Association's annual meeting here. The lizard-saliva drug is the subject of a co-development and marketing agreement between Eli Lilly & Co. of Indianapolis, and Amylin Pharmaceuticals Inc. of San Diego.
The Gila (pronounced HEE-luh) monster, is a poisonous lizard that burrows in sandy holes along the Gila River in Arizona in the American Southwest. It feeds as few as three times a year, and stores fat in its tail. In spring, it awakens from its torpor and grazes at night on eggs and small mammals -- incapacitating its prey with a venoumous bite.
But the drug-- a chemically synthesized copy of an ingredient in the critter's saliva -- is distinct from its toxic venom, the researchers said. The Gila monster isn't labeled as endangered, but zookeepers deem it vulnerable due to capture and human encroachments on its turf. In any case, the push to produce new diabetes therapies wouldn't imperil the lizards, becasue the drug is made in the Amylin labs and would have no environmental impact. Lilly has invested $425 milllion in stock and cash in Amylin, which hopes to file for regulatory approval for the drug in 2004.
In 63 volunteers with Type 2 dibetes, Amylin said the drug Exenatide, a synthetic copy of the lizard-saliva substance exendin-4, helped half of them lower their blood sugar to the target levels recommended for diabetics. Type 2 diabetes is a condition of high blood sugar linked to obesity and caused by the inability to utilize insulin.
Volunteers lost an average of about 5 pounds. The patients had been unable to conrol their blood sugar after three months on oral diabetes drugs such as metformin and sulfonylurea compounds. Such failure often presages the need to use insulin, said Alain Baron, Amylin's senior vice president of scientific affairs.
The test was an open-label study, without placebo controls. But the company has three continuing placebo-controllled trials of the drug in a total of 1,600 volunteers, the first due to deliver its results at the International Diabetes Federation meeting in Paris in August.
The twice-daily injections before breakfast and dinner had a "profound postprandial effect," Dr. Baron said in a session devoted to late-breaking clinical trials. The drug works by stimulating insulin secretion, slowing the movenent of food through the digestive tract, decreasing food intake, reducing weight gain and improving the function of insulin-producing beta cells in the pancreas.
Exenatide has one major drawback: nausea. Fully 27% of volunteers reported upset stomachs, mostly mild to moderate. Fourteen people dropped out of the study, six due to nausea. Another potential limitation: The drug had no impact on blood lipids cholesterol, a marker of the cardiovascular disease risk incurrred by diabetic people.
Mayer B. Davidson, University of California at Los Angeles professor, said many such compounds have emerged from a 40-year search by scientists to pierce the mysteries of hunger. First came the discovery of compounds dubbed incretins in the 1960s. "Now we have many hormones to choose from," Dr. Davidson said. The Gila monster drug, Dr. Davidson said, might be the first to reach the market.
The discovery that Gila monster saliva contained a compound similar to one found in the human digestive tract was made by a postdoctoral student, who was screening compounds made by venomous animals, Dr. Baron said.
People at risk for Type 2 diabetes have other options for weight loss and glycemic control. Among many presentations here, researchers from the University of Texas Health Science Center in San Antonio said Roche Group's weight-loss drug Xenical in combination with diet and lifestyle change helped reduce the incidence of Type 2 diabetes in people with precursor conditions to diabetes.
