A well-established family of drugs used to treat parasitic diseases is showing surprising potential as a therapy for tuberculosis (TB), according to new research from University of British Columbia microbiologists.
The findings, published online this week in the journal Antimicrobial Agents and Chemotherapy, are based on in vitro tests of the avermectin family of drugs. Discovered nearly 40 years ago, the drugs are commonly used in the developing world to eliminate the parasitic worms that cause river blindness and elephantiasis but have been thought to be ineffective against bacterial diseases. The UBC study shows that in the lab, the drugs actually killed the bacteria that cause TB, including drug resistant forms.
"These drugs are cheap, routinely produced by pharmaceutical companies, and, in many cases, approved for humans use," says UBC researcher Santiago Ramón-García, a co-author on the paper. "So the jump from lab bench to clinic could be much quicker."
"In addition, the drug concentrations effective in vitro indicate members of this family might be very valuable additions to the small repertoire of drugs we have to fight multi-drug resistant TB, which have very low probabilities of being cured."
The international collaboration was lead by scientists in UBC's Department of Microbiology and Immunology associated with UBC's Centre for Tuberculosis Research and the Neglected Global Diseases Initiative.
"This underscores the great potential for investments in research to find new uses for approved drugs or synergistic drug combinations," says co-author and UBC microbiologist Charles Thompson.
Further studies are needed to assess the drugs' clinical application for treating TB. UBC researchers are now working with animal models to determine effective dosage levels and regimens. They will also study whether avermectins could be combined with other drugs to create effective therapies.
The Avermectin Drug Family
Avermectins where discovered in the mid-1970s in an anti-nematode screening program led by the Kitasato Institute and the Merck, Sharpe and Dohme laboratories. Three members of the drug family – ivermectin, selamectin and moxidectin – are bactericidal against mycobacterial species, including multi- and extensively-drug resistant Mycobacterium tuberculosis. Ivermectin is approved for clinical use in humans, and selamectin for veterinary use. Moxidectin, already approved for veterinary use, recently passed clinical trials for human use.
Global Impact of TB
In 2011, 8.7 million people around the world contracted TB and 1.4 million died from it, according to the World Health Organization. While some countries are making progress in preventing and treating the disease, some strains of TB are notoriously resistant to antibiotics and few new therapies are in the pipeline.
Funding
The research was funded by the Canadian Institute of Health Research, the British Columbia Lung Association, Grand Challenges Canada – Stars in Global Health (funded by the Government of Canada), and the National Institutes of Health.
The UBC Neglected Global Diseases Initiative (NGDI)
Launched in 2009, the NGDI brings together top UBC researchers to study and develop treatment for infectious diseases of poverty, including HIV/AIDS, TB and malaria. Their work includes basic understanding of these diseases, vaccine and drug development, health care infrastructure and food security. Funding for research associated with the NGDI recently exceeded $20 million.
The UBC Centre for Tuberculosis Research (CTBR)
Founded in 2007, the CTBR works to understand the basis of TB's prevalence, including its inherent resistance to antibiotics, and to develop and optimize new anti-bacterials that target TB. CTBR researchers leverage expertise in microbiology, biochemistry, immunology and chemistry to better understand the biological significance of our discoveries and how these systems can be used as targets for new drugs for TB chemotherapy.
Journal
Antimicrobial Agents and Chemotherapy