Jørn
Bolstad Christensen, a chemist from the University of Copenhagen has obtained a patent for a
drug that can make previously multidrug-resistant bacteria once again
responsive to antibiotics. Christensen, together with doctors Jette Kristiansen
from the University of South Denmark and Oliver Hendricks from the King
Christian X’s Hospital for Rheumatic Diseases in Gråsten, Denmark, discovered
that Thioridazin, an antipsychotic drug, was able to kill bacteria without any
noticeably harmful effects upon humans.
Thioridazin, who’s chemical
name is 10-{2-[(RS)-1-Methylpiperidin-2-yl]ethyl}-2-methylsulfanyl
phenothiazine was registered as an
antipsychotic drug and used in the treatment of schizophrenia and psychosis,
but has also been reported to have antibacterial properties. Due to the many
side effects and cardiotoxicity, the drug Thioridazin has been withdrawn from
many countries and is no longer used for treatment of schizophrenia and
psychosis. The Thioridazine as included in the antiphychotic drug is a so
called ‘racemic mixture’, the combination of 50% (S)-thioridazine and 50% (R)-thioridazine.
The (S) and (R) indicate the two enantiomers or ‘mirror images’ of each other. Dr
Ruben Thanacoody, a physician at the Royal Infirmary Edinburgh, discovered that
it was the R-Thioridazine which was responsible for most of the anti-psychotic
activity, but that both R- and S-thioridazine were capable of inhibiting
bacterial growth. This was further substantiated by the study
from Christensen. Hence the idea was born to isolate the separate
S-thioridazine and use this as an antimicrobial agent.
(S)-Thioridazine’s own
antibacterial properties are not that spectacular, but other researchers from the
University of Southern Denmark revealed
what the actual effects of Thioridazine on the gene expression and cell wall
composition of a drug-resistant bacteria called Methicillin-Resistant
Staphylococcus aureus were. Thioridazine acts by blocking the efflux pump of
bacteria, which is responsible to pumping any unwanted chemicals out of the bacterial
cell. So if another antibacterial agent is given, due to the lack of ‘outflowing’
opportunities , the concentration of the other antibacterial agent within the
bacterial cell increases. Jørn Bolstad Christensen has put this idea into
practice and obtained said patent to pair (S-)Thioridazine and other
antibacterial agents.
If this drug (currently called
JEK 47) will become available in Europe, depends on the interest of investors
in this substance. “I would rather donate this discovery to an NGO able to use
this substance in poor countries that suffer from drug-resistance problems than
watch it collect dust in the industrialised world. So, I hope that an investor
comes along to develop this ground-breaking substance,” concludes Bolstad
Christensen.
