Researchers find possible treatment for cholesterol-storage disease
Last Updated: Monday, January 26, 2009 | 6:18 PM ET
CBC News
U.S. researchers have developed a compound they say may one day reverse Niemann-Pick Type C disease, an inherited neurodegenerative disorder that causes cholesterol to accumulate in cells, leading to brain damage and death.
John Dietschy and colleagues at the University of Texas Southwestern Medical Center at Dallas found that a single injection of a compound called CYCLO released the accumulated cholesterol in cells and reversed the disease in a mouse model.
If cholesterol within cells is not properly metabolized, the buildup leads to liver disease, a loss of fine motor skills and dementia. The vast majority of children diagnosed with Niemann-Pick Type C die before they are 20 years old and many before age 10. Few people diagnosed with it reach age 40.
In the lab, researchers injected CYCLO into seven-day-old mice with the Niemann-Pick mutation. Shortly after administration, the mice began to process cholesterol just as their health counterparts did, the researchers said.
After 49 days, the mice treated with a single injection continued to show substantially lower tissue cholesterol levels than the untreated mice, as well as improved liver function and decreased loss of functioning neurons.
Cholesterol in the body comes from dietary sources and is also made by the body itself. It's essential for many biological processes, including the construction and maintenance of cell membranes.
Dr. Dietschy, who has been studying cholesterol metabolism for nearly 50 years, cautioned that the findings in no way represent a cure for Niemann-Pick Type C.
"The key idea is that we appear to have overcome the transport defect in the lysosome that is brought about by the genetic defect or mutation," Dietschy said. "We do not yet understand what is happening at the molecular level, but it is clear that this compound somehow overcomes the genetic defect that causes individuals to accumulate cholesterol."
The researchers want to follow up with a study on how long the drug's effects last. They also want to determine how long they can extend the lifespan of lab animals who have the mutation.
"By treating at seven days, we eliminated approximately one-third of the accumulated cholesterol almost immediately," Dietschy said. "Now we want to see what happens if we give it every week. Can we maintain low cholesterol levels? That's what we're looking at now."
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