Exercise in a pill?
2008-08-01 09:15
Washington - Researchers who
genetically engineered "marathon mice" that could run for hours
have found two pills that can mimic the effects - and they
have already developed a test for the drugs in case athletes
try to cheat with them.
The drugs reproduce many of the biological benefits of
exercise, helping cells burn fat better and boosting endurance,
said Ronald Evans, a Howard Hughes Medical Institute researcher
at the Salk Institute for Biological Studies in California.
One of the pills may some day help people enhance their
exercise or training, while the other might be more suited for
couch potatoes who need to kick-start themselves, Evans and
colleagues reported on Thursday in the journal Cell.
"If you like exercise, you like the idea of getting more
bang for your buck," Evans said in a statement. "If you don't
like exercise, you love the idea of getting the benefits from a
pill."
In 2004, Evans and his colleagues genetically engineered
mice by tweaking a gene called PPAR-delta, a master regulator
of different genes.
Stayed lean
Gene-engineered mice could run twice as far
as normal mice and stayed lean even when fed a high-fat diet.
The next step was to find a drug that might mimic these
effects.
Evans tested a compound called GW1516, one of a family of
compounds that researchers are looking at as obesity and
diabetes drugs. But even though it affected the genes of the
mice, it did not affect their metabolism.
"There was no change at all in running performance. Nothing
- not even a percent," Evans said in a statement.
Then the researchers thought about what happens in real
life.
"If you're out of shape - and most of us are - and you
want to change, you have to do some exercise. The way we
reprogramme muscle in adults is by training."
So they trained the mice while some were on the drug and
others were not.
All the mice became more athletic but those given GW1516
ran 68% longer than those that had only done the
exercise training. "The dramatic effect of the drug was
stunning," Evans said.
AMPK activity
But that does not help people who might have muscle-wasting
diseases, fatigue, or who are too overweight to exercise.
They went back to see if there was a different way to
affect PPAR-delta.
One compound that is well understood already
is AMP-activate protein kinase or AMPK, "a master regulator of
cellular and organismal metabolism", they wrote.
"We think AMPK activity is the secret to allowing
PPAR-delta drugs to work," Evans said.
A drug called Aicar mimics AMP, Evans said, "so muscle
thinks it's burning fat."
Mice given Aicar ran 44% longer than untreated
animals, the researchers found.
"This is a drug that is like pharmacological exercise,"
Evans says. "After four weeks of receiving the drug, the mice
were behaving as if they'd been exercised."
Mass spectrometry test
Treated mice could outrun mice given traditional exercise
training, Evans said.
"Almost no one gets the recommended 40 minutes to an hour
per day of exercise," Evans said. "For this group of people, if
there was a way to mimic exercise, it would make the quality of
exercise that they do much more efficient."
The pills are only available experimentally now and Evans
is not working with any drug company. But GW1516 has a
relatively simple chemical structure and can be synthesised
easily, Evans said.
His team created a mass spectrometry test to detect the two
drugs and their metabolic by-products in the blood or urine.
They are working with the World Anti-Doping Agency to develop
the test, perhaps in time to retroactively test 2008 Olympic
athletes.