posted July 27, 2000 10:04 PM            

Jun 29, 16:12

Cancer Drug May Fight Fat

WASHINGTON, June 29 (UPI) -- A drug currently being tested as a cancer killer may also
work as a fat buster, researchers say.

If the compound works, it will offer a weapon with a completely new mode of action in the
escalating battle against obesity, investigators say.

One of the researchers involved in the study says it "drops weight like a stone," but did
not slow down metabolism, a normal reaction to cutting excess calories that spells doom for
most diets.

A scientific team from Baltimore's Johns Hopkins University had been studying the drug --
an enzyme blocker called C75 -- for more than a decade as a potential treatment for several
kinds of cancer.

One side effect of the drug -- the only one the scientists could find -- made it almost
impossible to continue research in live animals. Experimental mice stopped eating and lost
so much weight that they were in danger of starving to death. Dr. Frank Kuhajda says the
team, which included four separate divisions at Johns Hopkins, decided try it as a fat
fighter.

The scientists have started a small company called Fasgen, Inc. to speed up the
development of C75 as an anti-obesity compound. Nevertheless, it will take at least two
years before human studies can start, he says.

"The point of this company is to get this 1/8C75 3/8 into patients," say Kuhajda.

The compound now has to be injected, but it may be possible to package it in a pill.

The Johns Hopkins team, which published its findings in Friday's issue of the journal
Science, tried the compound in normal mice and those genetically engineered to be
excessively fat.

Both kinds of mice became thinner, some losing as much as 30 percent of their body weight
depending upon the dose of C75. It was a rapid drop, and the mice given C75 lost more
weight than those who were fasting.

The reason for this, Kuhajda says is that mice fed C75 did not develop a slower
metabolism, a biological mechanism designed to prevent starvation in times of famine
which has been the downfall of many a diet in the current era of excess.

"This compound inhibits feeding, but does not allow the metabolism to shut down. It tricks
the animal into thinking it's well fed," says Kuhajda.

"It drops weight like a stone," he says. The compound also reversed a fat-related form of
diabetes. C75 blocks a key enzyme called Fatty Acid Synthase, which functions as a kind
of fat-making machine, he says.

"This is the enzyme that turns your pasta into fat," Kuhajda told United Press
International.

FAS is the last enzyme on an assembly line of about 25 enzymes that builds fat molecules
to store energy. Kuhajda says that in a test tube, purified FAS will "make fat before your
eyes," if given the right building blocks.

This may have been very useful when primitive humans had to sprint across the savanna
and kill an animal for supper. In the age of the Big Mac, it has become a nuisance.

"It makes us fat," Kuhajda says.

The drug also appears to turn off production of a brain chemical called neuropeptide Y, a
popular target for obesity drug developers because it functions as an appetite on-off
switch.

Scientists had originally explored FAS as a target for cancer therapies because tumors
make, and seem to need, a lot of fat.

"Why cancer cells make so much fat is still an enigma to us," says Kuhajda. Turning off
FAS plunges tumor cells into a state known as apoptosis, also called cellular suicide.

Since the drug does not attack dividing cells as most chemotherapies do, it has none of the
side effects of conventional cancer treatments. Research on C75 as a cancer drug is still
underway.

Weight loss and lack of interest in food was the only limiting factor in the studies.

"We could only dose once a week, because the animals stopped eating," he says. Animals
regained their appetites and their weight when the treatments stopped.

Obesity expert Dr. Steven Heymsfield says, "The implications 1/8of the study3/8 are
profound."

Heymsfield is the deputy director of the Obesity Research Center at St. Luke's Roosevelt
Hospital Center in New York.

"This opens a new chapter," says Heymsfield, who was not involved in the study but
reviewed the Science paper. "I don't know of anything like this. It's very novel," he told
UPI.

But, Heymsfield, who has conducted clinical trials on other obesity drugs, including leptin
and Xenical, cautions that just because it makes animals stop eating doesn't necessarily
mean it will help trim hefty humans. There are many reasons, other than hunger, why
people overeat.

"Food tastes wonderful, it's plentiful, it's a source of social stimulation," he says. "We eat
dessert, a wonderful dessert, after we finish our meals when we couldn't possibly be
hungry."

Dr. Denise Bruner, an Arlington, Va.-based bariatric physican and president of the
American Society of Bariatric Physicians, which is based in Englewood, Col., says the
study is "very exciting." Bariatric physicians focus on treatment of obesity and related
health problems.

Bruner says it shows that scientists are now probing the molecular basis of the condition,
"as opposed to obesity being solely blamed on people's lack of willpower."

She says, however, that it's too early to know if this drug will be the answer to the problem
that everyone is looking for. Early studies on the hormone leptin were also extremely
promising, she says, but the drug was ultimately a disappointment. "Leptin was as exciting
at this stage, but it didn't pan out as the panacea. Not the magic bullet," she says.

posted July 28, 2000 08:32 AM            

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Nam Et Ipsa Scientia Potestas Est!

posted July 28, 2000 10:22 AM            

We may have to buy some stock in this company.

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LAte

posted July 31, 2000 01:14 PM            

Understanding obesity.....? I would argue that it will likely never happen for no other reason than the monetary potential that survives based on the lack of understanding.