SYSTEMIC GENE THERAPY IMPROVES LIFE SPAN,
MUSCLE FUNCTION IN MICE WITH MUSCULAR DYSTROPHY
TUCSON, Ariz., July 5, 2006 — Scientists at the University of
Washington-Seattle have for the first time markedly improved the well-being and
life span of mice with a severe form of muscular dystrophy by systemically
administering new genes for a missing protein, the Muscular Dystrophy
Association (MDA) announced today.
"The result is exciting because these severely affected mice
represent a high hurdle for gene therapy and more closely model the human form
of the disease Duchenne muscular dystrophy," said Sharon Hesterlee, MDA's
Director of Research Development.
In a paper published online today in the prestigious journal Nature
Medicine, a team led by MDA-supported Jeffrey Chamberlain, and including MDA
grantee Paul Gregorevic, describe how a single intravenous injection of highly
miniaturized (micro) genes for the muscle protein dystrophin restored muscle
structure and function to skeletal, heart and diaphragm muscles throughout the
bodies of the mice.
Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin and is the most common form of childhood
muscular dystrophy. Dystrophin's absence leads to progressive deterioration in
the strength of voluntary muscles, as well as the muscles controlling breathing
and heart function. It generally results in death by age 30. Because of its X
chromosome origins, DMD affects males almost exclusively, although female
carriers can also have symptoms.
The University of Washington researchers encased their
laboratory-engineered microdystrophin genes inside type 6 adeno-associated
viral (AAV) transport vehicles (vectors) and administered them to 1-month-old
mice missing not only dystrophin but another, similar protein, known as
utrophin. Without dystrophin or utrophin, mice develop a severely disabling
muscular dystrophy that closely resembles human DMD.
About four months after the gene injection, the investigators found
widespread dystrophin production in the diaphragm, which was then able to
resist contraction-induced injury almost as well as the diaphragm does in
healthy mice. Dystrophin was restored throughout the heart as well.
When the team looked at a leg muscle, they saw that dystrophin had
been restored and had increased muscle fiber size by 85 percent and muscle mass
by more than 90 percent, while improving force-producing capacity and
resistance to injury. The treated mice were able to use their running wheels,
whereas the untreated mice were not.
Eighty percent of the untreated mice in the experiments had died by
4 months of age, while the mice in the treated group were still alive at 10
months, when results were being analyzed.
"We feel this work supports the theory that gene therapy could be a
highly effective treatment for muscular dystrophy," Chamberlain said. "However,
the challenge now shifts to testing these methods in the clinic, which will
require careful studies to look at safety and practicality before we can
address effectiveness in patients."
MDA (www.mda.org) is a voluntary health agency
working to defeat more than 40 neuromuscular diseases through programs of
worldwide research, comprehensive services, and far-reaching professional and
public health education.
