Gene Therapy Builds Muscle in Mice
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.