Research points to new potential drug target in brain
PARKINSON'S
Sirtuins gained initial fame as enzymes involved in aging -- and thus as a focus of scientists' ongoing quest for eternal youth. Newly published work by researchers at the MassGeneral Institute for Neurodegenerative Disease suggests that one of the sirtuins, SIRT2, could also hold the key to new drugs against Parkinson's disease, Huntington's disease and possibly even Alzheimer's. With a bit of luck, said researcher Aleksey Kazantsev, human clinical trials of drugs based on his team's work could begin in just two or three years -- and yield the first really novel medications in a long time for Parkinson's, which affects about 1 million Americans. The research, published online in Science last week, builds on earlier findings by Kazantsev's team: that clumps of protein harm the brain in Parkinson's disease, and so consolidating them into blobs that are bigger but fewer in number could help stem the damage. As they tried to understand how the bigger blobs protected neurons, they found that suppressing the enzyme SIRT2 made the clumps less destructive. So they worked to find even more powerful ways to inhibit SIRT2, and succeeded. BOTTOM LINE: A promising new drug target has been found for Parkinson's disease. CAUTIONS: The findings are only from rat neurons and insect models of Parkinson's. It has not yet been shown that blocking the enzyme in a living mammal alleviates symptoms of Parkinson's. WHAT'S NEXT: Exploring the class of compounds that inhibit SIRT2 to develop an anti-Parkinson's drug. That could include further testing on existing compounds and designing new ones. WHERE TO FIND IT: www.scienceexpress.org
CAREY GOLDBERG
CANCER
Drug could help replenish blood stem cells faster
A fertile tropical fish and an obsolete stomach acid drug are the unlikely sources for a scientific breakthrough that may help chemotherapy and bone marrow transplant patients recover faster. Researchers at Children's Hospital Boston, eager to find better ways to replenish the blood stem cells crucial to the body's immune system and often depleted during cancer therapy, say they have identified a chemical that can increase such cells in zebrafish. Dr. Leonard Zon and colleagues tested more than 2,500 chemicals on embryos of the fish, which is prized by scientists because females can make hundreds of offspring in a single week and its blood system is similar to that of mammals. Observing stem cell production through the fishes' transparent skin, they noticed an increase in the cells in embryos that were soaked in a precursor of prostaglandin, a lipid created when the body is injured. The researchers then tested their hypothesis on mice by giving them bone marrow containing a stable version of prostaglandin developed in the 1980s to treat gastritis. Mice that received the treated marrow made three times more blood stem cells than those who got regular marrow, raising hopes that the compound could help human patients whose blood is slow to regenerate. "This chemical already existed, it was proven to be safe and has a strong activity," said Zon. "That makes you feel like there is a good chance of it being successful in humans."
BOTTOM LINE: Prostaglandins could help cancer patients replenish their blood cells.
CAUTIONS: What works in fish and mice might not work in humans.
WHAT'S NEXT: Zon and colleagues hope to collaborate with the Dana-Farber/Harvard Cancer Center on clinical trials for the drug next year, including testing whether it might make cord blood transplants more effective.
WHERE TO FIND IT: Nature, June 21
FELICIA MELLO 