JUPITER, Fla. – Scientists at The Scripps Research Institute may have found the first potentially effective therapy for human prion disease.
Prion diseases are caused by misfolded proteins in the brain. Creutzfeldt-Jakob Disease (CJD), sometimes called the human version of mad cow disease, affects about one person in every one million people per year worldwide, according to the National Institutes of Health. There are about 200 cases per year in the US, NIH reports.
Researchers have identified two drugs already approved for human use that show anti-prion activity, according to the Institute. The drugs, tacrolimus and astemizole, reduce the amount of the normal form of prion protein (PrP) at the cell surface. The disease distorts PrP.
Tacrolimus is widely used in organ transplantation, but may not be the best option for an anti-prion drug because of concerns about neurotoxicity, according to the Institute. Astemizole is an antihistamine that is widely available as a generic in more than 30 countries, according to the Institute. It appears to encourage autophagy, the process by which cells eliminate unwanted components.
“Autophagy is involved in several protein misfolding neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases,” said Prof. Corinne Lasmezas, lead scientist on the project. “So, future studies on the mode of action of astemizole may uncover potentially new therapeutic targets for prion diseases and similar disorders.”
The drug crosses the brain-blood barrier and is effective at relatively low concentrations, according to the Institute.
The study is "Unique Drug Screening Approach for Prion Diseases Identifies Tacrolimus and Astemizole as Antiprion Agents". Prof. Lasmezas collaborated with TSRI Prof. Emeritus Charles Weissmann and Peter Hodder, director of Lead Identification. The study was published online ahead of print by the journal Proceedings of the National Academy of Sciences.