Principal Investigator (PI)
Research Agency of Aragon (ARAID) & University of Zaragoza (UNIZAR)
The Foundation is providing £168,140 in support.
Santiago Ramón - Pilar Arenaz
GSK’s in kind contributions would be critical for the following: (i) Access to time-lapse microscopy and micro-pumping system to mimic PK profiles; (ii) imaging and analytical modeling software and skills; (iii) access to clinical data for modeling. In addition, based on previous experience (RIFACEPH project), the excellent scientific and personal support provided by GSK scientists would greatly facilitate the successful outcome of this proposal.
This proposal aligns and complements with current clinical trials now being explored by GSK DDW clinical partners. It also comes with additional funding that the applicant, Dr. Ramón-García, recently secured from the European Community for a 2-year project to be performed at GSK DDW.
Carbapenems and cephems are beta-lactam (BLMs) antibiotics with different anti-tuberculosis (TB) killing properties and phenotypic responses that might affect therapy design for optimal clinical outcomes (Figure 1). Understanding the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of BLMs alone and in combination with synergistic partners is critical if they are to be used for TB therapy (Figure 2). Similarly, the molecular determinants underlying synergistic interactions of BLMs with synergistic partner drugs are currently unknown. Elucidating the synergistic mode of action of such combinations will allow the design of novel strategies for TB therapy and help counteract the emergence of future resistance.
To answer these questions, time-lapse microscopy, in vitro microbiology assays and transcriptomic studies will be leveraged to provide high quality molecular and pre-clinical data that, through mathematical PKPD modeling based on completed and ongoing GSK DDW BLM-containing TB clinical trials, will inform the design of future human combination trials with BLM components.Campylobacter spp. and Salmonella spp.). Through this Open Lab project, this characteristic will be exploited for high-throughput screens against Shigella spp. and other enteric bacteria.