Potentially effective therapy for human prion disease identified

Washington , Thu, 04 Apr 2013 ANI
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Washington, April 4 (ANI): American researchers have for the first time identified a pair of drugs already approved for human use that effectively acts against prion disease.

Human diseases caused by misfolded proteins known as prions are some of most rare yet terrifying on the planet-incurable with disturbing symptoms that include dementia, personality shifts, hallucinations and coordination problems.

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, led by The Scripps Research Institute (TSRI) Professor Corinne Lasmezas and performed in collaboration with TSRI Professor Emeritus Charles Weissmann and Director of Lead Identification Peter Hodder, 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. Astemizole not only crosses the blood-brain barrier, but works effectively at a relatively low concentration.

Lasmezas noted that astemizole appears to stimulate 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," she said. "So future studies on the mode of action of astemizole may uncover potentially new therapeutic targets for prion diseases and similar disorders."

The study will be published in the journal Proceedings of the National Academy of Sciences. (ANI)

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