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Gene Therapy for Brain Ailments Reuters 1:25 p.m. Jun. 5, 2000 PDT WASHINGTON -- Using protective balls of fat and precisely targeted antibodies, researchers said on Monday they had found a way to sneak gene therapy into the brain in a new approach they hope could be used against a range of diseases from Alzheimer's to brain cancer. They said their new method might also be used in general as a safe and effective technique for gene therapy of all kinds. And, although they did their work in rats, they think their technique might be ready to be tested in humans within months. Dr. William Pardridge, a professor at the University of California Los Angeles School of Medicine, said gene therapy has not worked well in the past and attempts to make it work in the brain have been especially unsuccessful. "The reason all pharmaceutical companies have given up on gene therapy of the brain is it requires drilling a hole in your head -- that's expensive, invasive, and it doesn't work," Pardridge said in a telephone interview. "The gene only goes to a part of your brain the size of a pin head. The second problem is they uniformly use viruses, either adenoviruses or herpes viruses, and we all have a pre-existing immunity to either virus." The idea behind gene therapy is to correct disease or genetic defects by introducing new genes into the body. It is still highly experimental and the field suffered a setback last year when one patient died, apparently because his immune system revolted against the virus used to carry the genes. Writing in the Proceedings of the National Academy of Sciences, Pardridge's team said they had taken another standard gene therapy route, using capsules of fat known as liposomes. To target the liposomes, they attached antibodies, which are immune system compounds that can seek out and attach to specific cells, as well as viruses and bacteria. "This enables us one, to have widespread distribution and expression of the gene through the brain following a simple intravenous injection and two, no use of viruses," Pardridge said. "The DNA is encapsulated from the liposome so it is fully protected from all the enzymes that are there to chew it up." But just injecting DNA is no good, because it does not know where to go. That is where the antibodies come in. Pardridge's team used as their target the transferrin receptor, which is a molecule found on brain cells and on cells in certain other organs such as the liver. When injected into rats, it carried the DNA -- in this case simply an experimental "marker" gene that could easily be traced -- into brain and liver cells. Gene therapy in the brain might be used to treat or even cure Parkinson's disease, brain cancer, and genetic disorders such as Tay-Sachs and Gaucher's disease. Pardridge thinks the approach could be used against a range of other disease, too. "You can deliver anything you want to cells," he said. "It opens up an entirely new approach to pharmaceutics." But what was especially intriguing about this approach, he said, was it was able to get past the "blood-brain barrier" -- a molecular system that keeps many drugs from getting into brain cells. "Now we have found a way to ferry genes across the barrier by exploiting natural receptors in the brain." Pardridge hopes his team can move ahead quickly. "The next step is usually you say three to five years before studies in humans," he said. "That isn't the case here." He said his team had a project that could move into human beings within five months. But, he said, no drug companies were interested. "All of the components are available off the shelf now, but who is going to invest in this?" he asked. "It's a problem. You mention blood-brain barrier to venture capitalists and their eyes get glazed over."