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Drugs Activating PXR May Help In Treating Niemann-Pick type C disease

Scientists at Washington University School of Medicine in St. Louis and other institutions have reported that experimental findings suggest that drugs that activate// pregnane X receptor (PXR) my help in the treatment of Niemann-Pick type C (NPC) disease. NPC is progressive neurodegenerative disorder that is often fatal within the first two decades of life.

Scientists working with a mouse model for Niemann-Pick type C (NPC) disease showed that experimental treatments appear to be acting through the pregnane X receptor (PXR). Found in the cell nucleus, PXR regulates the activity of a cluster of genes that helps the body get rid of toxins.

NPC affects approximately one in every 100,000 children. Affected individuals typically present in early childhood with gait disturbance and progressive impairment of motor and intellectual function and usually die during adolescence. At present there are no effective treatment options.

Drugs already known to activate PXR include the anti-seizure drug dilantin, the antibiotic rifampicin and the herbal compound St. John's Wort. Additional experiments are underway in mice to firmly determine if the successful laboratory treatments are acting through PXR. If this proves to be the case, new clinical trials may soon follow, according to senior author Daniel S. Ory, M.D., associate professor of medicine and of cell biology and physiology.

"Because we have so few options to offer NPC patients and their families now, if this connection can be confirmed, we'd try to get some known activators of PXR into clinical trials as soon as possible," Ory says.

The results appear online this week in the Proceedings of the National Academy of Sciences.

NPC belongs to a broader class of diseases known as lysosomal storage disorders, which affect more than 30,000 people worldwide. In these disorders, disposal and recycling units within cells known as lysosomes become jammed, p
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