Quantitative Systems Pharmacology approaches for Development of
Host-Directed Therapies against Mycobacterium tuberculosis infections
Abstract
Host-directed therapies (HDT) that modulate host-pathogen interaction
offer an innovative strategy to combat Mycobacterium tuberculosis (Mtb)
infections. When combined with conventional anti-tuberculosis regimens,
HDT strategies could contribute to improving treatment outcomes,
reducing treatment duration, and preventing resistance development. It
is however challenging to evaluate the interplay of host-pathogen
interaction events in response to HDT strategies, and to translate
experimental findings towards patients. Quantitative understanding of
the multi-faceted nature of the host-pathogen interactions is vital to
rationally design HDT strategies. Here, we (1) provide an overview of
key host-pathogen interactions as basis for HDT strategies, (2) discuss
experimental models to characterize host-pathogen interactions relevant
for HDTs, and (3) discuss the utility and approaches of quantitative
systems pharmacology (QSP) models to inform design of HDT strategies
against Mtb infections. QSP models can be used to identify and optimize
treatment targets, to facilitate preclinical to humans translation, and
to design combination treatment strategies.