Discovery of new therapies for Buruli ulcer treatment
Researcher:
Ramón García, Santiago
Congress:
WHO Meeting on Buruli ulcer Control and Research
Participation type:
Comunicación oral
Other authors:
Alfonso Mendoza-Losana
Year:
2017
Location:
WHO Headquarters. Geneva, Switzerland
Standard treatment of Buruli ulcer (BU) involves 8 weeks of combination therapy with rifampicin and streptomycin. The daily painful injection of streptomycin together with the side effect associated, i.e. ototoxic, nephrotoxic, and hepatotoxic, in addition to issues related to pregnancy and treatment to young infants made the scientific community look for alternatives to streptomycin. Clarithromycin or moxifloxacin have now been proposed, although their effectiveness still needs to be clinically demonstrated. No alternatives for rifampin are, however, currently available, thus making it the corner stone drug for BU therapy; the emergency of rifampicin resistance in Mycobaterium ulcerans would virtually bring BU to the pre-antibiotic era.
Drug development for neglected diseases such as BU, mainly affecting developing countries, is especially complicated due to lack of interest from the main scientific community and, as a consequence, lack of investment. To overcome these limitations and speed up the discovery and development process of a much-needed new BU therapy we are applying knowledge gathered in tuberculosis (TB) R&D programs.
A collaborative effort between the University of British Columbia (Canada) and GlaxoSmithKline at the Diseases of the Developing World (GSK-DDW) campus in Spain has used two innovative and complementary approaches to identify new anti-BU therapies:
• Repurposing clinically approved antibiotics. We have identified promising antibiotics active alone and in synergistic combinations with rifampicin against M. ulcerans with a clinical pedigree, low toxicity, and orally and pediatric available.
• Screening a GSK in-house library of advance anti-TB drug candidates. We have identified promising compounds with activities in the nano molar range that are currently in pre-clinical development for TB therapy.
Our work here presented open new therapeutic avenues, both in the short term by optimizing current BU drug therapy and in the long term by identifying new alternatives to rifampicin treatment, that promise to be much more effective and less toxic that currently available treatments.
Standard treatment of Buruli ulcer (BU) involves 8 weeks of combination therapy with rifampicin and streptomycin. The daily painful injection of streptomycin together with the side effect associated, i.e. ototoxic, nephrotoxic, and hepatotoxic, in addition to issues related to pregnancy and treatment to young infants made the scientific community look for alternatives to streptomycin. Clarithromycin or moxifloxacin have now been proposed, although their effectiveness still needs to be clinically demonstrated. No alternatives for rifampin are, however, currently available, thus making it the corner stone drug for BU therapy; the emergency of rifampicin resistance in Mycobaterium ulcerans would virtually bring BU to the pre-antibiotic era.
Drug development for neglected diseases such as BU, mainly affecting developing countries, is especially complicated due to lack of interest from the main scientific community and, as a consequence, lack of investment. To overcome these limitations and speed up the discovery and development process of a much-needed new BU therapy we are applying knowledge gathered in tuberculosis (TB) R&D programs.
A collaborative effort between the University of British Columbia (Canada) and GlaxoSmithKline at the Diseases of the Developing World (GSK-DDW) campus in Spain has used two innovative and complementary approaches to identify new anti-BU therapies:
• Repurposing clinically approved antibiotics. We have identified promising antibiotics active alone and in synergistic combinations with rifampicin against M. ulcerans with a clinical pedigree, low toxicity, and orally and pediatric available.
• Screening a GSK in-house library of advance anti-TB drug candidates. We have identified promising compounds with activities in the nano molar range that are currently in pre-clinical development for TB therapy.
Our work here presented open new therapeutic avenues, both in the short term by optimizing current BU drug therapy and in the long term by identifying new alternatives to rifampicin treatment, that promise to be much more effective and less toxic that currently available treatments.