NEWS OF THE WEEK PHARMACEUTICAL
RESEARCH
POTENTIAL NEW USE FOR PACLITAXEL Cancer-fighting agent shows early promise as an Alzheimer's treatment
T
HE WIDELY USED CANCER
drug paclitaxel (Taxol) has the potential to treat neurodegenerative disorders such as Alzheimer's disease, according to a preclinical proof-of-concept trial performed in mice [Proc. Natl. Acad. Sci. USA, published online Dec. 20, http://wwwpnas.org/cgi/ doi/10.1073/pnas.040636ll02}. The research was spearheaded by John Q. Trojanowski, director of the Institute on Aging at the University of Pennsylvania School ofMedicine, with support from Angiotech Pharmaceuticals, a manufacturer ofpaclitaxel. Trojanowski, who has been working with microtubule-stabilizing compounds for decades, says this is the first study to confirm the potential of microtubule-stabilizing compounds as a new class
FUELS
of drugs for treating neurodegenerative diseases. Paclitaxel and other microtubule-binding drugs, such as the epothilones and the discodermolides, combat cancer by stabilizing a cancer cell's microtubules, thereby blocking cell division and causing the cells to die. Similarly, a protein called tau stabilizes the microtubule networks that act as a highway for axons in nerve cells. In neurodegenerative diseases like Alzheimer's, tau proteins become misfolded and form tangles in the brain's nerve cells. Without tau to stabilize the microtubules in the network, the transmission of nerve signals is lost. 'Think of tau as the cross-tie of the microtubule train track," Trojanowski explains. "The tracks will handle the traffic as long as they
POLICY
LIQUEFIED NATURAL GAS RISKS ASSESSED Heavy damage from tanker breach could affect wide area, analysis finds
S
ERIOUS INJURY AND HEAVY
property damage from fires and explosions caused by a large breach in a liquefied natural gas (LNG) cargo tank could affect areas more than one-quarter mile from the tanker ship, says a recent analysis by Sandia National Laboratories, Albuquerque, N.M. Lesser injuries and damage could occur more thanamilefromthe release site, according to the report. HTTP://WWW. CEN-0NLINE.ORG
There are currently four U.S. marine LNG terminals, Sandia says, but more than 40 new terminals are being considered because of high U.S. natural gas use and domestic shortages, major concerns ofthe chemical industry U.S. natural gas imports are expected to more than double over the next 20 years, and nearly all new gas imports will be LNG—a 28-fold increase, according to the
are parallel. If the cross-ties are missing, the tracks will wobble, and the train will run off the tracks." The Perm research team demonstrated that in mice genetically engineered to have misfolded tau, paclitaxel can substitute for the microtubule-binding protein, thereby restoring the nerve signal network. This approach of trying to offset the loss of protein function is a novel way to tackle Alzheimer's, Trojanowski points out. Most other approaches aim to prevent or Paclitaxel (Taxol) break up the aggregated proteins and plaques that characterize the disease, he explains. The researchers say work needs to be done to create microtubule-binding compounds that cross the blood-brain barrier. But because paclitaxel is already approved to treat cancer, Trojanowski is hopeful that the drug and similarly approved microtubule-binding agents will move quickly into clinical trials for treating neurodegenerative disorders.— BETHANY HALFORD Department ofEnergy Terminals are proposed for major population centers on all three U.S. coasts. The report models overall risk and provides approaches to limit risk of an LNG accident or intentional breaching. Risk from an accident is small and manageable with current safety practices, the report says. An intentional event—such as a terrorist attack—would cause a larger breach and do more damage, but that risk can be reduced with security planning and mitigation, according to the report. In the past 40 years, more than 80,000 LNG carrier shipments have occurred worldwide without major accidents, the report says. Eight marine incidents have resulted in spills but no fires.—
Even without immediate ignition, Sandia says, a cloud of LNG vapor has thepotential for causing fires or explosions up to a mile and a half from a leaking tanker.
JEFF JOHNSON
C & E N / J A N U A R Y 3. 2005
9
