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Researchers Discover Weight-Loss Peptide

In their presentation, investigators from Unigene Laboratories described an experiment comparing UGL269 with PYY and placebo in dogs. PYY is a pancreatic peptide which, based on animal studies, is believed to suppress appetite.

The search for weight loss therapies is as old as medicine itself. Small molecule treatments are marginally effective or cause undesirable side effects, some of which may be serious. Unigene Laboratories, a Boonton, New Jersey-based biopharmaceutical company, has reported on a novel approach to hunger suppression based on naturally occurring peptides.

Scientists from Unigene Laboratories presented animal data on a new molecule, UGL269, at the Keystone Symposium Conference, “Obesity: Novel Aspects of the Regulation of Body Weight,” held in Alberta, Canada on January 22. Designed by Unigene researchers, patent-pending UGL269 is an analog of a natural peptide hormone.

In their presentation, investigators described an experiment comparing UGL269 with an analog of PYY and placebo in dogs. PYY is a pancreatic peptide which, based on animal studies, is believed to suppress appetite. UGL269 and PYY were formulated identically. Both contained an absorption enhancer and a protease inhibitor to limit digestion of the peptides in the digestive tract. The placebo contained all the excipients except for the peptides.

Dogs were monitored for food intake before, during, and after the dosing period. At equivalent doses, UGL269 significantly decreased food intake throughout the treatment period of one week, while PYY exhibited a smaller effect. The food intake of dogs given a placebo remained unchanged. Dogs receiving UGL269 also showed a small but significant weight reduction whereas dogs receiving the same dose of PYY experienced barely noticeable weight loss. Both food and water intake returned to pre-dose levels during the one week washout period following the dosing period. Dogs given placebo capsules exhibited a slight increase in both food intake and weight.

“Therapies that modify feeding behavior and result in weight loss represent a significant unmet medical need,” commented Dr. Warren Levy, President and CEO of Unigene. “UGL269 may offer a new, orally administered approach for weight loss through appetite reduction.”

Obesity has reached epidemic proportions in developed countries, and in the United States in particular. Data from the Centers for Disease Control and Prevention suggest that the prevalence of people who are overweight has risen in the U.S. from the 10-13% range in 1991 to approximately 33%, for both men and women. Obesity is a risk factor for a number of serious medical conditions, including cancer and cardiovascular disease. It is also a predisposing factor in the development of Type 2 diabetes, a condition that independently leads to diseases of the kidneys, eyes, and heart/circulatory systems to name a few. Diabetes care costs the U.S. healthcare system tens of billions of dollars per year, and the U.S. economy billions of hours in lost productivity.

Small-molecule weight loss drugs have a spotty history. Many are stimulants and one, the popular phentremine (“Phen-Fen”), caused serious heart valve problems. Other systemically-acting diet drugs appear to cross the blood-brain barrier, and have been implicated in depression and mood changes. Fat-blocking drugs cause less serious side effects (fatty stools, discharge), but since they are barely more effective than diet alone, these agents have not caught on as developers had hoped.

Peptides, by contrast, are natural molecules. ULG-269 uses only naturally-occurring amino acids. If broken down in the body these peptide building blocks will be used in the same manner as if they were ingested as food.

ULG-269 is produced in E. coli through Unigene’s patented Secrapep® manufacturing technology. Secrapep provides a robust, scalable production platform for numerous peptide pharmaceuticals, including salmon calcitonin, parathyroid hormone analogs and several glucose regulatory peptides.

Peptide drugs are usually administered to patients by injection instead of in pill form because the digestive system breaks these molecules down into smaller peptides and amino acids, rendering them inactive. Through Unigene’s Enteripep® oral delivery technology, peptide drugs are protected from the digestive enzymes and acids in the stomach and small intestine, and are absorbed into the system like any other drug.

“The goal for our program was to develop a novel peptide that was composed of natural building blocks and with the ability to reduce food intake in a superior manner to PYY, and ULG-269 satisfies both criteria,” comments Dr. Levy. “Further studies will determine whether we have discovered a more natural approach for reducing food intake with fewer side effects than existing approaches. We are fortunate that our manufacturing and drug delivery capabilities position us to exploit this opportunity, in the hopes of developing a reasonably priced, orally administered tablet.”

Janet Vasquez | Newswise Science News
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