Dairyquinolones for Tuberculosis
There is a new drug in the armamentarium against
tuberculosis which also appears to work on dormant Mycobacteria
which are normally not affected by routine antitubercular drugs.
Dairyquinolones inhibit the mycobacterial ATP synthetase; the enzyme which
remains active even in the dormant bacteria. The efficacy in humans was
confirmed in a recent phase 2 randomized controlled trial conducted on 47
patients with newly diagnosed multidrug-resistant
pulmonary tuberculosis. The rate of conversion to a negative culture was
48% in the dairyquinolone (TMC207) group (10 of 21 patients) and 9%
in the placebo group (2 of 23 patients). TMC207 also
reduced the time to culture conversion: the probability of becoming
culture negative on any given day within the 8 weeks of the trial was 11.8
times higher. Dairyquinolone TMC207 appears to work synergistically with
routine antitubercular therapy and might be instrumental in reducing the
duration of drug therapy and improving efficacy of current regimens almost
5 times (NEJM 360:2397-2405, June 2009).
Why Edaxadiene is so Exciting?
Decoding any riddle needs an eye for minutiae. The
enduring puzzle of how Mycobacterium tuberculosis has been plaguing
humankind for eons and how man can finally befool it, is now being tackled
from a whole new angle. Reuben Peters from Illinois University first
started to wonder why Mycobac-terium bovis is so much less
infective to humans as compared to Mycobacterium tuberculosis. The
genetic make up of the two is 99.9% identical. Peters found that the
Mycobacterium tuberculosis produces a defensive molecule that prevents
the macrophage cells from destroying them. Peters and his team called this
molecule ‘edaxadiene’. The next step was to try to find molecules that
bind with the edaxadiene-producing enzymes from tuberculosis and
neutralize them. This makes the tuberculosis cells unable to produce
edaxadiene. Without edaxadiene, tuberculosis cells would have a reduced
ability to resist being killed by the macrophage cells. Peter’s group has
now found edaxadiene enzyme inhibitors which are effective in
vitro. The big leap will be to see their efficacy in vivo.
Since edaxadiene seems to be specific for humans, finding an appropriate
animal model will be one of the big challenges. ( J Biol Chem 28 August
2009, Medical News Today 2 October 2009).
Online Free Refresher Course for MDR Tuberculosis
The World Medical Association in its annual assembly in
New Delhi launched a free online course in MDR TB. The new course, which
incorporates key elements of internationally accepted strategies for
management and control of TB, will link to the WMA’s MDR-TB course which
has been running for the past two years. It is free of charge and can be
used by physicians in private practice as well as in the public.
Physicians will be able to receive credits for completing the course as
part of their continuing medical education program. (http://www.wma.net/en/70education/10onlinecourses/10mdr_tb/index.html)