The Scientist: Dr. Santiago Ramón-García is a Research Associate in Charles Thompson’s lab (Department of Microbiology & Immunology and the Center for Tuberculosis Research) at the University of British Columbia (UBC), Canada. At UBC, Santiago has developed a new screening approach for tuberculosis (TB) drug discovery based on the identification of synergistic combinations of drugs already approved for clinical use.
The sponsor: The University of British Columbia (UBC), established in 1908, is one of the top leading research universities in Canada and worldwide. TB research at UBC expands from basic to translational projects aiming to understand both the molecular mechanism of antibiotic resistance and infection used by Mycobacterium tuberculosis, the causative bacterial agent of TB, and to develop novel TB therapeutics.
Foundation funding: The Foundation is providing £ 170,240 in support, together with co-funding from the European Union FP7 program through its COFUND scheme.
GSK’s contribution: GSK is providing expertise and in-kind contributions in High Throughput Assays (HTA), in vitro pharmacokinetic and pharmacodynamic (PK/PD) modeling, and pre-clinical in vivo TB models. GSK is also providing access to Biosafety Level 3 facilities and GSK’s collection of compounds.
Project Description: One approach to generate new TB treatment options in a timely and cost-effective manner is “repurposing” clinically used drugs with known pharmacokinetic and safety data; thus allowing for rapid evaluation in clinical trials. In addition, drug repurposing is a strategy that would allow for an easier long-term implementation since manufacturing and distribution infrastructure is already established.
Rifampin (RIF) is a cornerstone drug in TB therapy, having both bactericidal and sterilizing activity. Numerous in vitro, in vivo and clinical investigations suggest that there is a direct relation between RIF dose increase and efficacy, but use of higher doses is limited by the toxicity profile. Thus, if higher efficacy could be achieved for a given dose of RIF by augmenting it’s anti-tuberculosis activity TB therapy could be potentially shortened, reducing the rate of TB transmission, and the development of resistant strains.
At UBC, Dr. Ramón-García identified conventional antibiotics that enhance RIF’s in vitro activity. His work at GSK will further explore the synergistic drug interactions of RIF using GSK’s collection of compounds. Santiago will pre-clinically develop those compounds originally identified at UBC in addition to new leads generated at GSK.