Common antihistamine could be treatment for prion diseases
23 April 2013
Scientists from the Scripps Research Institute (TSRI) in Florida
have for the first time identified a pair of drugs already approved
for human use that show anti-prion activity and, for one of them,
great promise in treating these universally fatal disorders.
Prions cause some of most rare yet terrifying diseases that are
incurable and have 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
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% 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
However, astemizole is an antihistamine that has potential for
use as an anti-prion drug. While withdrawn voluntarily from the US
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.
Lasmézas 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
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 Aβ peptides and
helps mediate a number of critical deleterious processes in animal
models of the disease.
Karapetyan YE et al. Unique drug screening approach for prion
diseases identifies tacrolimus and astemizole as antiprion agents.
PNAS 2013 110 (17) 6609-6610; doi:10.1073/iti1713110