The most well-known of these is Creutzfeldt-Jakob disease, which can be described as the naturally occurring human equivalent of mad cow disease.
The new study used an innovative high-throughput screening technique to uncover compounds that decrease the amount of the normal form of the prion protein (PrP, which becomes distorted by the disease) at the cell surface. The scientists found two compounds that reduced PrP on cell surfaces by approximately 70 percent in the screening and follow up tests.
The two compounds are already marketed as the drugs tacrolimus and astemizole.
Tacrolimus is an immune suppressant widely used in organ transplantation. Tacrolimus could prove problematic as an anti-prion drug, however, because of issues including possible neurotoxicity.However, astemizole is an antihistamine that has potential for use as an anti-prion drug. While withdrawn voluntarily from the U.S. over-the-counter market in 1999 because of rare cardiac arrhythmias when used in high doses, it has been available in generic form in more than 30 countries and has a well-established safety profile. Astemizole not only crosses the blood-brain barrier, but works effectively at a relatively low concentration.
The study noted that eliminating cell surface PrP expression could also be a potentially new approach to treat Alzheimer’s disease, which is characterized by the build-up of amyloid β plaque in the brain. PrP is a cell surface receptor for Aß peptides and helps mediate a number of critical deleterious processes in animal models of the disease.The first author of the study, “Unique Drug Screening Approach for Prion Diseases Identifies Tacrolimus and Astemizole as Antiprion Agents,” is Yervand Eduard Karapetyan of The Scripps Research Institute. Other authors include Gian Franco Sferrazza, Minghai Zhou, Gregory Ottenberg, Timothy Spicer, Peter Chase, Mohammad Fallahi, Peter Hodder and Charles Weissmann of The Scripps Research Institute. For more information on the study, see http://www.pnas.org/content/early/2013/03/29/1303510110.abstract
Eric Sauter | EurekAlert!
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