Current issue
Cancer ‘miracle’ drug Gleevec may also work in Alzheimer’s animal studies suggest
BY JOSEPH BONNER
When Gleevec was swiftly approved by the Food
and Drug Administration in 2001, it revolutionized the treatment of
a form of leukemia, proving more than twice as effective as
existing drugs. Since then, it has also shown exceptional results
in the treatment of some types of gastrointestinal cancers. And
now, a team of Rockefeller researchers says it may be able to slow
the progression of Alzheimer’s disease.
Already, there’s been a lot of excitement
surrounding Gleevec. It made front page headlines when it first
went on the market two years ago as a treatment for chronic myeloid
leukemia; many declared a new era in the treatment of cancer. The
reason: Gleevec represents a new class of cancer treatment drugs
that work by targeting a mutant enzyme that causes normal cells to
become cancerous. Because it’s so specific, Gleevec is
generally more effective and causes fewer side effects than more
traditional chemotherapy drugs that kill both cancerous and
non-cancerous cells.
That Gleevec soon would prove safe and
effective for treating people with another form of cancer —
gastrointestinal stromal tumors — attracted more headlines.
What else could this “miracle drug” combat?
Alzheimer’s disease, theorized a Rockefeller University research team headed by
Paul Greengard, Nobel laureate and director of the Fisher Center for
Alzheimer’s Disease Research. They theorized that the drug
might target related proteins that contribute to the formation of
the plaques that characterize Alzheimer’s disease by causing
healthy nerve cells to weaken and die.
“We knew that Gleevec binds to at least
four enzymes that are distantly related to one another in
evolutionary terms, so we took a gamble that there might be
more,” explains William Netzer, a research associate in
Greengard’s lab who was the first author of a Proceedings of the National Academy of Sciences paper describing the research.
To test their theory, the scientists injected
Gleevec into laboratory cultures of brain cells obtained from mice.
The drug indeed reduced the buildup of small molecules that lead to
the formation of plaques. What’s more, neither
Gleevec nor another related compound the scientists studied
suffered from the same stumbling block that had ruled out many
other promising agents in the treatment of Alzheimer’s
— a tendency to interfere with proteins crucial to the
body’s immune system.
Taking the research a step further, the
Rockefeller researchers, and their colleagues at Memorial
Sloan-Kettering Cancer Center, injected Gleevec into the spinal
fluid of guinea pigs, whose brain chemistry is similar to that of
humans. The results were the same: plaque-forming molecules were
reduced in the treated animals.
“The safety of Gleevec, which has already
been shown through its use in treating chronic myeloid leukemia and
gastrointestinal stromal tumors, combined with its inability to
inhibit immune function, make this class of compounds an attractive
lead for the development of a potentially safe treatment for
Alzheimer’s,” says Greengard, who is a Vincent Astor
Professor and a recipient of the 2000 Nobel Prize in Physiology or
Medicine.
Whether Gleevec will prove to be uniquely
beneficial to people with Alzheimer’s cannot be determined
until several kinks are ironed out. The biggest hurdle: The
relatively large molecules that make up Gleevec do not cross the
blood-brain barrier, the gatekeeper that protects the brain. In the
animal studies, Gleevec had to be injected directly into the spinal
fluid — a workaround that is obviously less than ideal for
humans.
“It’s possible that Gleevec could
be chemically modified to cross the blood-brain barrier,”
says Netzer. “Or there may be other compounds that function
like Gleevec but are chemically suited to enter the brain.”
October 31, 2003
|
