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Contact: Elaine Schmidt ([email protected])
310.794.2272 or 310.794.0777
UCLA researchers have developed the first non-invasive method for delivering therapeutic genes into the brain -- an innovation that could help millions of people suffering from Parkinson's disease, brain cancer and AIDS, as well as genetic disorders such as Tay-Sachs and Gaucher's disease. The findings were published in today's early edition of Proceedings of the National Academy of Sciences.
"Gene therapy of the brain has historically been hampered by the presence of the blood-brain barrier -- the capillary wall that prevents the brain's uptake of therapeutic compounds from the bloodstream," explained Dr. William Pardridge, a professor at the UCLA School of Medicine and principal investigator. "Now we have found a way to ferry genes across the barrier by exploiting natural receptors in the brain."
Earlier scientific attempts to cross the barrier have included drilling holes through the skull to introduce external genes or injecting irritating substances into the carotid artery to disrupt the barrier's protective properties. In addition to proving largely unsuccessful, these efforts are highly invasive and impractical for physicians to administer to patients, who often require a lifetime of treatment.
Certain antibodies shown to bind to the brain's natural receptors possess the potential to deliver attached genes into the brain. However, scientists have repeatedly stumbled in their efforts to package the desired DNA in a form that remains stable in the bloodstream.
Pardridge and his colleagues overcame this obstacle by coating gene-bearing fatty particles, called liposomes, with several thousand waxy strands that serve dual functions: (1) to increase the stability and duration of the liposomes in the bloodstream, and (2) to tether the liposomes to the brain-targeting antibodies.
After injecting rats intravenously with the antibody-coated liposomes, the researchers observed that two different genes crossed both the blood-brain barrier and brain-cell membranes. Plus, the system achieved success with a significantly smaller quantity of gene product than ever previously reported.
"We packaged the liposomes with a gene that expresses a blue marker to reveal gene expression in the brain," Pardridge explained. "Normal brain tissue appears entirely pale white. But when we examined the rats' brains following injection, we saw each neural structure outlined in vivid blue. That means that the brain had absorbed the liposomes and was already expressing the genes in its cells."
According to Pardridge, this approach to brain gene therapy could be transferred to people by exploiting antibodies that target human receptors. "The practical tools to conduct brain gene therapy in humans already exist," Pardridge noted. "We have genetically engineered antibodies for use in humans that should be ten times more effective than in rats."
For a copy of the journal article, please contact the National Academy of Sciences news office at (202) 334-2138 or view the text at http://www.pnas.org/papbyrecent.shtml.
To interview Pardridge or to receive a BMP or TIFF file of the brain expressing the blue genetic marker, please contact Elaine Schmidt of UCLA Health Sciences Communications at (310) 794-0777.
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