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The newspaper of The Johns Hopkins University December 3, 2007 | Vol. 37 No. 13
 
Researchers Get $250,000 Grant to Pursue Down Treatment

By Audrey Huang
Johns Hopkins Medicine

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."

 

Related Web sites

Reeves Lab at Johns Hopkins
Down Syndrome Research and Treatment Foundation

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