NIAID supports clinical testing of anti-cancer drug for TB
The National Institute of Allergy and Infectious Diseases has awarded a three-year $5 million grant to an international team of investigators to test the anti-cancer drug imatinib as a repurposed treatment for tuberculosis. The study will take place at Emory University in Atlanta, and in South Africa at the Aurum Institute's Tembisa Clinical Research Center in South Africa.
The study builds on the work of Daniel Kalman, PhD and
colleagues at Emory and at the Center of Disease Control and
Prevention, who showed that imatinib, known commercially as
Gleevec, disrupts the machinery that tuberculosis bacteria
exploit when they infect human cells. Imatinib is particaulry
effective at low doses, where it additionally stimulates a host
anti-pathogen immune response that the tuberculosis bacteria
tries to suppress.
Imatinib is FDA-approved for use
against chronic myelogenous leukemia and gastrointestinal
stromal tumors. It was one of the first examples of "targeted
therapy," aimed at specific genetic changes in cancer cells
driving growth. Imatinib became available in generic form in
2016.
Kalman heads a team that includes Edmund
Waller, MD, PhD, Cindy Giver, PhD., and Rabin Tirouvanziam PhD
at Winship Cancer Institute and Emory University School of
Medicine, Greg Bisson MD, PhD, at University of Pennsylvania,
Robert Wallis, MD from the Aurum Institute in South Africa,
Deepak Kaushal, PhD at Tulane University, Tawanda Gumbo, MD from
Baylor and Helen Fletcher, PhD from London School of Hygiene and
Tropical Medicine.
The investigators will assess the
safety and immune effects of low-dose imatinib in healthy human
volunteers, and then move to South Africa where the drug will be
tested in combination with standard antibiotic regimens in
patients with active TB. Plans call for 60 patients in the
United States and 195 in South Africa.
TB remains a
major public health threat, killing 1.4 million per year, mostly
in developing nations. The impact is especially severe in people
who are HIV-positive. Of additional concern, TB has evolved to
become resistant to some or all available antibiotics, and about
400,000 per year die from infections caused by these
strains. Lancet Infectious Diseases reports that China,
India, Russia and South Africa have the highest burden of
multiple drug-resistant tuberculosis.
Because
imatinib targets the host and not the pathogen, it will likely
prove effective against antibiotic-resistant TB, and will not
easily engender resistance itself. Kalman notes.
"There
is an urgent need for new drugs to treat TB," he says. "We are
fast approaching the day when all available antibiotics will
prove useless. This study is proof-of concept for imatinib in
antibiotic-sensitive TB. But if successful, our eventual goal is
to use imatinib against antibiotic resistant TB. Having new
immunomodulatory host-directed therapeutics that can complement
antibiotics would be an important, timely and welcome addition
to the anti-TB arsenal."
Source:
Emory University
