CJD cure - Stanley Prusiner's paper
james at pc.jaring.my
Tue Aug 14 13:51:32 EST 2001
On Mon, 13 Aug 2001 06:21:41 -0400, Ben Ayed
<hasdrubal at MailAndNews.com> wrote:
>According to the "mail on Sunday" issue of Aug 12 2001, Stanley Prusiner has
>just perfected a radical cure against CJD. The paper says he's going to
>publish the results in a scientific magazine. Could somebody inform me about
>what magazine it is? One of my relative is afflicted with this decease.
Here is the abstract. It appears Chlorpromazine and Quinacrine are the
top candidates. What a stroke of luck, two very well-used drugs can be
used to treat the disease. It is unclear if it is a cure but maybe
just a chronic treatment.
Proc. Natl. Acad. Sci. USA, Vol. 98, Issue 17, August 14, 2001
Acridine and phenothiazine derivatives as pharmacotherapeutics for
Carsten Korth, Barnaby C. H. May, Fred E. Cohen and Stanley B.
Institute for Neurodegenerative Diseases and Departments of Cellular
and Molecular Pharmacology, Biochemistry and Biophysics, Medicine, and
Neurology, University of California, San Francisco, CA 94143
Prion diseases in humans and animals are invariably fatal. Prions are
composed of a disease-causing isoform (PrPSc) of the normal host prion
protein (PrPC) and replicate by stimulating the conversion of PrPC
into nascent PrPSc. We report here that tricyclic derivatives of
acridine and phenothiazine exhibit half-maximal inhibition of PrPSc
formation at effective concentrations (EC50) between 0.3 µM and 3 µM
in cultured cells chronically infected with prions. The EC50 for
chlorpromazine was 3 µM, whereas quinacrine was 10 times more potent.
A variety of 9-substituted, acridine-based analogues of quinacrine
were synthesized, which demonstrated variable antiprion potencies
similar to those of chlorpromazine and emphasized the importance of
the side chain in mediating the inhibition of PrPSc formation. Thus,
our studies show that tricyclic compounds with an aliphatic side chain
at the middle ring moiety constitute a new class of antiprion
reagents. Because quinacrine and chlorpromazine have been used in
humans for many years as antimalarial and antipsychotic drugs,
respectively, and are known to pass the blood-brain barrier, we
suggest that they are immediate candidates for the treatment of
Creutzfeldt-Jakob disease and other prion diseases.
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