Gene Therapy Builds Muscle in Mice
By PAUL RECER=
AP Science Writer=
WASHINGTON (AP) _ Injecting new genes into aging muscles can
restore youthful vigor and strength, according to a laboratory
study of mice. But researchers caution that many safety questions
must be resolved before they can try the therapy on humans.
Old mice gained 27 percent of the muscle lost to age when
they
were injected with a gene that prompts muscle cell growth, the
researchers at the University of Pennsylvania Medical Center said
Monday.
For younger mice, the gain was about 15 percent, said Dr. H.
Lee
Sweeney, the study's senior author.
Before the technique is ready for humans, however, there are
both ethical and safety questions to be resolved, Sweeney said. For
athletes, he said, the injections could be the ``perfect
performance enhancer.''
``You build muscle mass and strength even without exercise,''
said Sweeney. ``And it is not detectable in the blood.''
Olympic athletes are routinely tested for drugs that
artificially improve strength and performance. Most such drugs are
now outlawed.
The safety issue arises because the same gene that causes
muscles to grow can also cause the overgrowth of unwanted cells.
``Abnormal growth could be a health risk,'' said Sweeney.
``For
instance, you wouldn't want your heart to grow larger.''
Nonetheless, the experimental gene therapy offers the promise
of
correcting one of the major problems of aging _ muscle feebleness,
the researcher said.
Some experts estimate that humans lose 10 percent of their
muscle strength and mass each decade after the age of 50. Weakness
from old age can cause falls, broken bones and loss of the ability
to walk or care for oneself.
This feebleness may be caused because the muscles stop making
a
protein called insulin-like growth factor-1, or IGF-1, which causes
new cells to grow,
In muscle tissue, that protein sends a signal to satellite
cells, which are immature cells within the muscle tissue. The
signal turns the satellite cells into functional muscle cells,
which then replace damaged or weaken tissue.
Without the IGF-1 signal, muscle cells that wear out or
become
injured are not replaced and a person becomes weaker.
To deliver the growth factor gene, the researchers used what
is
called an adeno-associated virus. The scientists first stripped the
virus of any genes that would cause disease, then inserted the gene
for the growth factor.
When it was injected into mouse muscle, the altered virus
quickly infected nearby cells, delivering the growth factor gene
but causing no other infection.
Once in place, the new gene caused the muscles to make IGF-1,
which, in turn, led to more muscles.
But the therapy worked only in the muscles directly receiving
the injection. It would thus be ``cumbersome'' and take scores of
injections to treat each muscle in the body, the researcher said.
``Instead, you would inject only into the muscles necessary
for
walking or other daily functions,'' said Sweeney. ``For the
majority of the elderly population, the border line between being
able to walk or not can be dealt with by targeting key muscle
groups.''
The experimental gene therapy next will be tested on rabbits
and
then on monkeys. Even if those studies go smoothly, Sweeney said,
it will be at least two years before the gene therapy is ready for
human experiments.
The researchers would first like to use the technique on
patients with a mild form of muscular dystrophy, said Sweeney.
But Dr. Leon Charash of Cornell University, a prominent
researcher in muscular diseases and a medical adviser to the
Muscular Dystrophy Association, said he doubted the gene therapy
would have much effect on muscular dystrophy.
``It might enhance the strength of the aging population,'' he
said. ``But that will have to be very cautiously done.''
A previous experimental use of IGF-1 injections to treat Lou
Gehrig's disease resulted in no side effects but also no dramatic
benefits. Lou Gehrig's disease includes degeneration of the nervous
system and muscle weakness.
Sweeney presented his study at a San Francisco meeting of the
American Society for Cell Biology. The study is to appear next week
in the Proceedings of the National Academy of Sciences, a
scientific journal.