The Down Syndrome Research and Treatment Foundation
has awarded a $250,000 grant to
Roger H. Reeves, a professor of physiology and a
member of the
McKusick-Nathans Institute of
Genetic Medicine at Johns Hopkins. Reeves and his
research team will extend their current studies on
a potential drug to see if its positive effects can improve
brain development in mouse models of Down
syndrome.
"The DSRTF award allows us to pursue our preliminary
observations immediately without the
now considerable delay that's usually associated with
obtaining federal funding," Reeves said. "With a
decrease of nearly 70 percent--from $42 million to $13
million--in the amount of Down syndrome
research dollars from the National Institutes of Health in
the last few years, the role of groups like
DSRTF has become critical to continued progress in the
effort to help 350,000 Americans with Down
syndrome."
Down syndrome results from inheriting three, rather
than the usual two, copies of chromosome
21, a condition known as trisomy 21 or Ts21. During
development, Ts21 causes the cerebellum, the part
of the brain that coordinates movement and participates in
motor learning, to grow too slowly,
resulting in a small and underdeveloped structure.
A key reason why the cerebellum doesn't grow fast
enough, according to Reeves, is that trisomic
cells do not respond to a natural growth factor called
Sonic hedgehog. "Sonic is one of the most
important signals that promotes proliferation of cerebellar
cells," Reeves said. "The cerebellar cells in
trisomic mice, however, don't respond as well to this
important signal."
Reeves' team discovered that injecting a potential
drug called SAG, which stands for sonic
agonist, can overcome the reduced response to Sonic and
cause trisomic brain cells to grow more
normally. In fact, injecting SAG only once allows the
cerebellum to grow properly through the first
third of its development.
"We're really anxious to see if the SAG injections
will result in an adult cerebellum with the
normal number of cells," Reeves said. "We also want to know
if other parts of the brain are affected."
To do this, the team will go back to the Ts21 mice and
inject them at different times during
development with different amounts of SAG. They then will
count brain cells in the cerebellum to
determine the best time of development for treatment to
achieve the best growth. Finally, adult mice
will be tested for improved learning and memory skills.
Michael Harpold, chief executive officer of the Down
Syndrome Research and Treatment
Foundation, said, "DSRTF is extremely pleased to award this
major new DSRTF research grant to Dr.
Reeves, which will allow his research group to rapidly
extend and expand their groundbreaking
research to investigate a novel potential therapeutic
target specifically related to an impairment in
neurogenesis and brain development in Down syndrome. A
critically important aspect of the research
supported by this grant also focuses on the evaluation of
positive functional outcomes, particularly
concerning improvements in learning and memory. Such
outcomes represent important criteria for the
ultimate goal of developing effective new therapies in Down
syndrome."