ARIA news reported in WSJ:
I bet we see 4 by end of day..
Rory
Ariad Pharmaceuticals Inc.
The Wall Street Journal -- January 4, 1999
Technology & Health:
Gene-Therapy Advance Is Made
By Ariad and University Team
----
By Robert Langreth
Staff Reporter of The Wall Street Journal
Researchers have overcome a major obstacle that has kept gene therapy from progressing into
everyday patient care. The advance could lead to a new type of gene therapy that would replace
existing injectable treatments for anemia, diabetes or cancer with a simple pill.
Scientists at the University of Pennsylvania and Ariad Pharmaceuticals Inc. have devised a new
method to deliver into laboratory animals a gene that produces a natural protein, EPO, which
stimulates the production of red blood cells. Specifically, with a single injection, the gene stays in the
body and can produce the protein for a year or more-in contrast to current treatments, which
typically require protein injections several times a week. However, the gene isn't switched on, and
remains dormant, until an oral drug is administered, allowing for fine control of how much protein is
produced.
Indeed, if the new technique works in people, it could become a competitive threat to some
important biotechnology drugs that are injected. Particularly vulnerable would be injectable EPO,
which is sold under different names by Johnson & Johnson and Amgen Inc. for the treatment of
anemia, though the two companies are working on improved versions of their EPO drugs. Annual
world-wide sales of injected EPO are about $3.5 billion.
Moreover, because the new method is potentially more convenient and safer than injectable drugs, it
could ultimately replace other injected therapeutic proteins such as interferon for hepatitis or cancer,
or even insulin for diabetes, researchers said. "We think [gene therapy] will ultimately be a safer and
more effective method than giving therapeutic proteins" with injections, said James Wilson, who
directs the Institute for Human Gene Therapy at the University of Pennsylvania and helped conduct
the new gene-therapy study. The results of the experiment are detailed in the Jan. 1 issue of the
journal Science.
Ariad, a Cambridge, Mass., biotechnology company working with the University of Pennsylvania to
commercialize the technology, has competition. Merck & Co. is also working on similar
gene-delivery methods, and it has done similar animal experiments with several other proteins,
including leptin for regulating body weight, according to Thomas Caskey, who heads gene-therapy
research at the drug giant. Merck won't disclose the other therapeutic proteins it is testing, pending
publication of its results in a major scientific journal.
Scientists cautioned that the new gene-therapy method is still in very early stages of development, and
emphasized that allimportant human tests haven't begun.
The new method could help solve some of the problems that have long plagued gene therapy, which
is esentially administering human genes to treat diseases. When the first human gene-therapy tests
started nearly 10 years ago, there was great hope that gene therapy would quickly ameliorate or cure
diseases ranging from cystic fibrosis to cancer. But initial experiments mostly ended in
disappointment, as the new genes were either ineffective, caused harmful side effects, or were
destroyed by the immune system before they had a chance to do much good.
For gene therapy to work for many chronic diseases, scientists needed a way to deliver new genes
for long periods of time without risk of them being destroyed by the immune system. But they also
sought a way to quickly turn off the genes in case a patient developed an unanticipated side effect. "It
is very important" to have a way to turn genes on and off, said Merck's Dr. Caskey.
To develop their new method, the University of Pennsylvania and Ariad scientists first inserted the
EPO gene into a harmless virus called AAV. Unlike other viruses that were used in earlier
gene-therapy experiments, this virus doesn't generate a particularly aggressive immune response,
allowing the genes to survive inside the body for long periods. But the scientists also added to the
virus, among other things, a molecular switch that ensures that the EPO gene can only be activated in
the presence of a drug called rapamycin.
Then, the researchers gave laboratory animals a single injection of the altered virus. The EPO gene
remained dormant until the animals were given rapamycin, thus switching on production of the EPO
protein. As long as the animals kept taking rapamycin every few days, the gene continuously
produced EPO.
Ultimately, human patients might be able to get a gene injection for EPO once every couple of years,
then merely take a pill every few days to activate the gene; the precise dose of EPO could be
controlled by raising and lowering the amount of rapamycin given. The method might allow for a
constant level of EPO to be produced, as opposed to the peaks and valleys of protein concentration
that can occur with existing injection therapy. Ariad and the University of Pennsylvania say they hope
to begin human tests of the method in a couple of years.
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