Researchers Sneak Gene Therapy Into Brain
By Maggie Fox, Health and Science Correspondent
http://dailynews.yahoo.com/h/nm/20000605/sc/cancer_brain_1.html
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
to invest in this?'' he asked. ``It's a problem. You mention blood-brain
barrier to venture capitalists and their eyes get glazed over.''
Copyright © 2000 Reuters Limited.
--
Judith Richards, London, Ontario, Canada
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