Old drugs for new variant CJD
Mepacrine and chlorpromazine, both of which have been
available for many years, could prove to be effective treatments for diseases
caused by prions, such as new variant Creutzfeldt-Jakob disease (nvCJD).
This theory has been proposed by Professor Stanley
Prusiner and colleagues, from the Institute of Neurodegenerative Diseases
at the University of California.
They showed that when either drug was added to neuroblastoma
cells infected with prions in vitro, the formation of a misfolded,
pathogenic prion protein, thought to be the cause of prion diseases, was
inhibited.
It is not known how the two drugs inhibit the formation
of the misfolded prion but their activity seems to be related to their
structure — both have a tricyclic “scaffold”, with a side chain extending
from the middle ring. The researchers say: “The structure-activity relationships
... described here should be useful in developing even more potent tricyclic
compounds for treating prion diseases.”
Professor Prusiner and colleagues say that mepacrine
and chlorpromazine are candidates for “immediate treatment” of nvCJD and
other diseases caused by prions, because they have been used to treat
chronic diseases for many years at a range of doses.
It is not known whether the two drugs act synergistically
and could be used in combination, nor is it known whether they could be
used for prophylaxis as well as treatment of people known to be infected
with prions (Proceedings of the National Academy of Sciences 2001;98:9836).
Mepacrine is an antimalarial drug that is sometimes
used for treatment of giardia and discoid lupus erythematosus, although
both uses are unlicensed. Chlorpromazine is an antipsychotic.
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