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A step toward controlling Huntington's disease?
Date:6/23/2011

al of this approach is to prevent the mutant HTT from being expressed in the brain and potentially slow, if not stop, the disease's march. Although cell and animal models have shown promise, Margolis and other researchers worry that getting just the right amount of DNA into the right portions of the brain may be a difficult or risky task, likely involving injections into cerebral spinal fluid or the brain itself. The feasibility of this approach remains unknown, he adds.

The new study suggests an alternative focus manipulating the newly identified natural "brake" with a drug so that more of the brake is made, which can then specifically stop or slow production of the huntingtin protein. "Whether it's possible to do this and do it safely remains to be seen," Margolis says, "but this gives us another approach to explore."

On the strand of DNA opposite the huntingtin gene, the researchers found another gene, which they named huntingtin antisense. This gene also includes the Huntington's disease mutation. In normal brain tissue and in cells growing in the laboratory without the Huntington's disease mutation, Margolis and his team determined that huntingtin antisense acts to inhibit the amount of huntingtin gene that is expressed. But in brain tissue and cells with the Huntington's disease mutation, there is less huntingtin antisense gene expressed, so the biochemical foot is essentially taken off the brake, leaving a toxic amount of huntingtin protein. Reapplying the brake, by experimentally altering cells grown in culture so that they express a large amount of huntingtin antisense, decreased the amount of the toxic huntingtin protein.

Huntington's disease was first described in the medical literature in 1872, but it wasn't until 1993 that the gene mutation was discovered "with hopes that the discovery would quickly lead to treatment," Margolis says. But the disease has proven unexpectedly complicated, with dozens of different pathways impl
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Contact: Stephanie Desmon
sdesmon1@jhmi.edu
410-955-8665
Johns Hopkins Medical Institutions
Source:Eurekalert

Page: 1 2 3

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