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Researchers at Johns Hopkins University, Md., have
discovered that verapamil, a drug normally used to treat high blood pressure,
accelerates TB treatment time when added to the antibiotic regimen. Since
treatment interruption creates drug resistance, the researchers believe a
shorter treatment time will improve treatment adherence and prevent resistant
strains.
According to Shasank Gupta, Ph.D., lead study investigator
and immunologist, verapamil, a calcium channel blocker, functions as an efflux
pump inhibitor, making bacteria more susceptible to antibiotics and destruction
by immune cell macrophages. It is not known exactly how the drug works but
another study showed that increased efflux pump action helped TB drug tolerance
and reduced the effectiveness of antibiotics.
From January to November 2012, the researchers conducted a
study in which TB-infected mice were treated with daily doses of isoniazid,
rifampin, and pyrazinamide for two months followed by daily isoniazid and
rifampin for four months. For six months, half of the mice received daily doses
of verapamil, equivalent to the minimum dose for humans. The mice receiving
verapamil were cured in four months compared to the normal six months.
Verapamil increased the destruction of TB bacteria 10-fold after two months.
After four months, half of the lung tissue samples from the mice receiving
verapamil had zero bacteria, while samples from those mice treated with the
standard antibiotics only were still positive for TB.
Clinical trials will begin in India later this year for a
safety study to determine the minimum effective dose of verapamil necessary as
add-on therapy for TB.
The full report, “Acceleration of Tuberculosis Treatment by
Adjunctive Therapy with Verapamil as an Efflux Inhibitor,” was published online
in the American Journal of Respiratory and Critical Care Medicine
(doi:10.1164/rccm.201304-0650OC).
