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Internaf Newsletter June 2000 Issue Page 3
Researchers
Sneak Gene Therapy Into Brain
By Maggie Fox, Health and Science
Correspondent WASHINGTON, June 5, 2000 (Reuters)
- 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 Copyright © 2000 Reuters Limited.
Todays Research...Tomorrows Cure
Internaf Newsletter June 2000 Issue Page 3 |