GERON
NEWS OF THE W EEK
FDA CLEARS STEM CELL CLINICAL TRIAL BIOMEDICAL RESEARCH: Testing
in humans is a milestone in a field fraught with controversy
T Human embryonic stem cells are grown in nutrientrich culture media, shown here being changed inside a biological safety hood.
HE FOOD & DRUG Administration has given
Geron, a small California-based biotech company, the green light to inject living cells manufactured from human embryonic stem cells into a handful of patients with spinal cord injuries. The trials, set to begin this summer, will be the first in the world to test the safety of a therapy derived from human embryonic stem cells in people. A lot of hope is riding on the outcome of the trials. If the product, called GRNOPC1, proves safe, it could open the door for other embryonic-stem-cell-based therapies to treat conditions such as juvenile diabetes, cancer, multiple sclerosis, and stroke, experts say. FDA’s decision “marks the dawn of a new era in medical therapeutics,” Thomas B. Okarma, president and CEO of Geron, said during a briefing. GRNOPC1 is intended to “permanently reverse disease pathology,
MAKING A TOXIN SYNTHESIS: Researchers build a poisonous lipid found in mussels
A
QUIRKY LIPID that is associated with seafood toxicity has been constructed in a lab for the first time. The work opens the possibility of developing tools to detect and study the molecule. First isolated from mussels in the Adriatic Sea, the compound is “a chemical oddity” because it’s a lipid that features both a sulfate group and six chlorine atoms, which is unusual, says Erick M. Carreira, a chemist OSO3H at the Swiss Federal Institute of Technology, Zurich, Cl Cl who led the research. He and coCl workers report the synthesis in Nature (2009, 457, 573). Cl Cl Cl The toxin probably originates from algae that are consumed by the mussel, explains Chlorosulfolipid Ernesto Fattorusso, a pharmacologist at the University of Naples Federico II who isolated the chlorosulfolipid in 1999. “But we were only able to extract a few milligrams,” Fattorusso says. “This synthesis appears relatively simple, considering the stereochemical complexity of the molecule,” so there are hopes of obtaining enough of it for extensive biological studies. Researchers are uncertain whether this compound is WWW.C EN-ONLINE .ORG
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not merely to temporarily relieve symptoms,” he noted. The therapy involves the use of growth factors that turn embryonic stem cells into oligodendrocyte precursor cells. Those precursor cells have been shown to repair myelin, or insulation, around nerve cells and to stimulate nerve fibers of laboratory animals with spinal cord injuries, thereby leading to restoration of function, Okarma said. Geron’s announcement marks a new chapter in the history of embryonic stem cell research, which has been fraught with controversy over how the cells are derived. Scientists have also disagreed over how to create highly purified products from cells that can turn into any type of human cell, says Michael D. West, founder of Geron and CEO of BioTime. But some critics say it is premature to test embryonic-stem-cell-based therapies in humans. “I think this decision plays on the desperateness of people with spinal cord injuries. It’s pretty hard looking at the rat research to say this is going to be a slam dunk,” says Jaydee Hanson, policy director of the nonprofit International Center for Technology Assessment. FDA’s approval comes as proponents of this area of research are eagerly awaiting the Obama Administration’s promised repeal of the current limitation on federal funding for human embryonic stem cell research.— BRITT ERICKSON
a direct toxic agent in cases of seafood poisoning. The synthesis could help them make this determination. Moreover, the synthesis will allow investigators to examine other biological roles of chlorosulfolipids, such as being a component of algae cell membranes, writes Christopher D. Vanderwal of the University of California, Irvine, in an associated Nature commentary. “I’m interested in finding out why nature would put chlorines in a lipid at all,” Carreira says. Vanderwal also notes that the 10-step synthetic strategy that produced the unusual lipids is “simple and direct, but seems to be the result of painstaking experimentation.” “There were a lot of dead ends,” Carreira says. But students Christian Nilewski and Roger W. Geisser reached their synthetic goal by employing alkene dichlorination reactions and an epoxide ring-opening sequence. The ring-opening step led to a “chemical surprise,” Carreira notes. Normally, epoxides undergo ring opening with an inversion of configuration at the carbon that is being attacked, but here the team observed retention of configuration. It turns out that the chloride-induced epoxide opening proceeds by double inversion, Carreira explains. “There are many interesting mechanistic curiosities to be explored in this system,” he adds. Because the synthesis is not enantioselective, Carreira says that he and his colleagues will next work to develop an enantioselective version of the procedure, as well as syntheses of other chlorosulfolipids.—SARAH EVERTS
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