Researchers find drugs with anti-prion activity

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Prion diseases such as Creutzfeldt-Jakob disease (CJD) in humans are known to be terminal and untreatable, but scientists at The Scripps Research Institute (TSRI) in Florida have found two drugs, already approved for human use, that have activity against the misfolded proteins. A variant form of CJD has been linked to consumption of beef from cattle infected with the prion disease Bovine Spongiform Encephalopathy (BSE).

The scientists found two drugs, tacrolimus and astemizole compounds that reduced the amount of the normal form of the prion protein (PrP) on cell surfaces by approximately 70 percent.

Of the two drugs, astemizole holds the greatest potential as a treatment, according to a TSRI news release.  Tacrolimus is an immune suppressant used in organ transplantation, but has risks including neurotoxicity. Astemizole is an antihistamine that was voluntarily withdrawn from the U.S. over-the-counter market in 1999 because of rare cardiac arrhythmias when used in high doses. It has, however, been widely available in more than 30 countries and has a well-established safety record. Astemizole crosses the blood-brain barrier and works effectively at a relatively low concentration, according to TSRI.
The researchers say astemizole appears to stimulate autophagy, the process by which cells eliminate unwanted components, and which is involved in neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases. Continued research on the drug could identify treatments for several related diseases.  



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