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Archive - Jun 1, 2011

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Hedgehog-Signaling Inhibitor May Permit Successful Transplantation of “Marginal” Livers

New research raises the possibility that the critically short supply of livers for organ donation could be expanded by treating so-called "marginal" livers with a substance that protects them from damage after being connected to recipients' blood supplies. The report appeared on April 14, 2011, in the journal Molecular Pharmaceutics. Dr. Ram Mahato and colleagues noted that the need for liver transplants has grown over the years, though the number of available livers has not. Currently, more than 16,000 people are waiting for a liver in the U.S., but fewer than 7,000 liver transplants were performed during the entire year of 2010. This shortage has led organ transplant teams to consider using marginal, or damaged, livers, such as those with cholestasis — a build-up of bile. But transplanting a damaged liver has risks, including a higher risk that the organ will fail. To overcome this challenge, the researchers utilized a hedgehog-signaling inhibitor to increase the odds of a successful liver transplant. They found that a compound called cyclopamine prevented further injury to cholestatic livers after the blood supply was cut off then returned — a situation similar to what transplanted livers undergo. The research was performed in rats, which are stand-ins for humans in the laboratory. It provided "convincing evidence" that cyclopamine may protect cholestatic livers from additional damage after a transplant procedure and improve clinical outcomes for the patients. [Press release] [Molecular Pharmaceutics abstract]

Potential New Drugs Based on Peptides

Who would have thought that Gila monster saliva would be the inspiration for a blockbuster new drug for Type 2 diabetes, or that medicines for chronic pain, heart attacks, high blood pressure, and stroke would emerge from venom of the Magician's cone snail, the saw-scaled viper, the Brazilian lancehead snake, and the Southeastern pygmy rattlesnake? These are just some of the sources contributing to the emergence of potential new drugs based on "peptides" that is the topic of the cover story in the May 30, 2011 edition of Chemical & Engineering News (C&EN), the American Chemical Society’s weekly newsmagazine. Peptides are short sequences of amino acids that are the building blocks of proteins. C&EN Senior Correspondent Ann Thayer explains that peptides play central roles in many key body processes involved in health and disease. As drugs, they have several advantages over traditional medications, including higher potency and lower toxicity. However, efforts to enlist peptides more extensively in medical treatment have stumbled due to peptides' short duration of action, tendency to be digested by enzymes in the stomach, and other problems. Thayer describes advances in overcoming those problems with 60 peptide drugs sold worldwide having sales of $13 billion in 2010 and scores of others in the pipeline. Some of the most successful of those already in use are based on peptides found naturally in animals like the Gila monster. A companion article describes how manufacturers are stepping up production, collaborating with peptide discovery companies. Peptide drugs are now longer and more complex than those developed earlier, but improvements have made production faster and more cost-effective. [Press release]