Back to Headlines and Presentations
A case of raging hormones? UW scientist's theory on diseases of aging being put to test
By JOHN FAUBER
Posted: Sept. 17, 2005
Madison - Craig Atwood thinks he knows why most of us will get old
and die. And it's all about sex.
The maverick University of Wisconsin-Madison researcher is convinced
that's the secret of why cancer cells might spread through our
organs, why our hearts someday might fail and why our brains might be
short-circuited by Alzheimer's disease.
His theory soon will be tested in two large, yearlong clinical trials
of a novel Alzheimer's drug, according to a company founded by the
doctor who developed the theory with Atwood. The Food and Drug
Administration has approved the trials, the company said in documents
filed this month.
Voyager Pharmaceutical plans an initial public stock offering to
raise as much as $129 million to help fund the trials and to advance
its research on using its drug to treat prostate cancer and brain
cancer. It has enlisted Tommy G. Thompson, the former Wisconsin
governor and former secretary of the U.S. Department of Health and
Human Services, to serve on the company's board of directors.
In their paper published last year in the journal Gerontology, Atwood
and co-author Richard Bowen titled the idea "Living and Dying for
Sex." Simply stated, they say hormones that regulate sexual
reproduction early in life can act in a harmful manner later in life,
generally when people reach their 40s. That happens because in an
attempt to maintain reproduction, the hormones futilely stimulate
cells in the body to divide, resulting in cell damage and disease.
Beginning later this year, a total of 1,100 people with mild to
moderate Alzheimer's disease will be enrolled in the two trials,
which will be a major test of the theory's validity.
"That's going to be the proof," said Donald Ingram, a scientist with
the National Institute on Aging, part of the part National Institutes
Out of the mainstream
"No one has come up with anything that contradicts this idea, that
reproduction and longevity are coupled," Atwood said in an interview.
But the idea remains far out of the mainstream, said Ingram, who is
not a part of the research.
"It's like a little tributary trying to find its way to the sea," he
Still, the theory is based on some sound scientific ideas, Ingram
said. He noted that humankind has defeated a lot of the environmental
forces, such as germs and poor nutrition, that used to kill people
earlier in life.
"We are not evolved to live such long lives," Ingram said. "There is
no genetic program to keep us staying vital past a certain age."
The scientific concept of hormonal wear and tear, which the theory
taps into, has been around for years, Ingram added.
Aubrey de Grey, a biomedical gerontologist at the University of
Cambridge in England, said of the theory: "It is consistent with what
we know, and therefore, it's well worthy of further detailed
The theory's main weakness is that it says only that reproductive
hormones have some effect on aging, not specifically how much, said
de Grey, who is not associated with Bowen and Atwood.
Different view on Alzheimer's
Equally out of the mainstream is their view of what causes
Alzheimer's disease. Even the company Bowen co-founded acknowledges
that its theory has not gained the wide acceptance of the prevailing
view: that the disorder is caused by the buildup of beta-amyloid
protein in the brain. Much of Alzheimer's research focuses on
preventing beta-amyloid from forming or clearing it from the brain.
Voyager Pharmaceutical's drug works in a completely different way, by
reducing the levels of sex hormones that Atwood and Bowen think are
causing damage to brain cells.
In public documents, the company released unpublished data from
smaller clinical trials it conducted, suggesting that its drug might
stabilize Alzheimer's patients.
The results are promising, but questions remain, said William Thies,
vice president of medical and scientific affairs at the Alzheimer's
With plans to enroll 1,100 patients, the trials will be among the
largest Phase 3 Alzheimer's drug trials when they begin this year, he
said. Phase 3 trials are large, double-blind trials designed to prove
the effectiveness of a therapy. In general, successful Phase 3 trials
are needed before a drug can be approved.
It's also likely to be expensive, as much as $300 million, he said.
"If they prove this does stabilize Alzheimer's disease, they will
have done a wonderful thing," Thies said. "If not, they will have
spent a lot of money."
Piero Antuono, an Alzheimer's specialist at the Medical College of
Wisconsin, said the earlier trial results, although involving only a
small number of patients, seem to show a significant benefit.
The current line of Alzheimer's drugs affects levels of certain
neurotransmitters, chemicals made in brain cells that can facilitate
memory. And those drugs have only a modest effect.
"Hormones are a totally different class of drugs than we've seen
before," said Antuono, a professor of neurology.
At the same time, Voyager is looking into the treatment of other
diseases, including prostate cancer, brain cancer, amyotrophic
lateral sclerosis (Lou Gehrig's disease) and disorders that occur in
infants who are born prematurely, according to a document filed Sept.
9 with the Securities and Exchange Commission.
For Atwood, an assistant professor of medicine at UW, the Alzheimer's
trials represent the culmination of several years of work developing
a controversial - some say revolutionary - theory of why people age.
He has lectured on the theory but made few converts. Atwood and
Bowen, who also serves as chairman and chief scientific officer of
Voyager Pharmaceutical, which is based in Raleigh, N.C., have sent
manuscripts to prominent scientific journals such as Nature and
Science, only to have them rejected.
Even UW, which recruited Atwood and where he has worked for two
years, has yet to promote his work, although Atwood's laboratory
program at UW and the VA Hospital in Madison has about 10 people who
work on various aspects of the theory.
"We've become very frustrated," said Atwood, who owns stock in
Voyager and is a company consultant. "We thought people would sit up
However, with the FDA's approval of the Phase 3 Alzheimer's trials,
they now are getting the attention of researchers.
Atwood said Bowen stumbled upon the idea several years ago when a
prostate cancer patient who also had Alzheimer's saw his Alzheimer's
symptoms become stabilized after he started taking the drug
leuprolide acetate, which has been used for more than 20 years to
treat conditions such as prostate cancer, endometriosis and
For Alzheimer's, their theory works something like this:
Adult brain cells generally do not divide and replicate. However,
when those cells continually are stimulated to divide by certain sex
hormones, it can result in damage to those cells, leading to
The main culprit, according to Atwood and Voyager Pharmaceutical, is
luteinizing hormone, a substance made in the pituitary gland that
helps regulate production of testosterone and estrogen. Research
suggests that levels of luteinizing hormone go up significantly later
In addition to stimulating brain cells to abnormally divide,
luteinizing hormone might promote the process that leads to
production of beta-amyloid in the brain. Leuprolide acetate
dramatically lowers levels of luteinizing hormone. The drug also
brings down testosterone and estrogen.
In its earlier clinical trials, Voyager used an injectable form of
leuprolide acetate. Since then it has developed an implantable form
of the drug, called Memryte, that provides sustained, long-term
release of the drug.
The Phase 3 clinical trials will use Memryte along with some existing
drugs that provide modest benefits in treating the symptoms, but not
the cause, of Alzheimer's.
One trial with as many as 550 patients will take place in the United
States, Canada and South America. The other trial also will enroll
550 patients and will take place mainly in Europe. UW, which took
part in the Phase 2 trial, could be a site for the next phase as well.
From the Sept. 18, 2005, editions of the Milwaukee Journal Sentinel
Have an opinion on this story? Write a letter to the editor or start
an online forum.