A CUNNING way of sneaking genes into the brain should make it easier to give
people gene therapies for diseases such as Parkinson’s and Alzheimer’s.
The brain is protected from potentially dangerous substances in the blood by
the tight junctions between capillary cells. Only recognised molecules are
allowed in, so to get genes into the brain, researchers either have to inject
them through holes drilled into the skull or give them intravenously along with
drugs that disrupt the blood-brain barrier.
Now William Pardridge and Ningya Shi at the University of California School
of Medicine in Los Angeles have found a way to trick the barrier into letting
therapeutic genes through while still protecting against harmful substances. The
researchers first packaged the genes inside a fatty sphere called a liposome.
Advertisement
Pardridge and Shi then tethered this package to an antibody that latches onto
receptors on the brain’s capillary cells and tells the cells to let the package
into the brain. “It piggybacks through without interfering with the endogenous
transport system,” says Pardridge.
When the researchers injected a package containing a gene for luciferase into
rats’ bloodstream, they found the protein appeared throughout the animals’
brains. Their results will appear in a forthcoming issue of Proceedings of the
National Academy of Sciences.
“This approach is intriguing, and a potentially useful means of distributing
genes widely throughout the brain,” says Mark Tuszynski, a neuroscientist at the
University of California, San Diego. Pardridge says they have already developed
antibodies for primate receptors that could work in humans.