SPERANDIO Brice

Our project aims at preventing and treating mucosal infections, and situations of conflict between the host and its microbiota, by developing a disruptive technology based on immuno-stimulatory molecules that selectively boost the expression of inducible antimicrobial peptides (AMP) of the innate immune system, naturally produced at mucosal surfaces. To face the problem of antibiotic resistance, this high-potential technology may be relevant both in situations of endemic infections in the developing world, and infectious or inflammatory pathologies in industrialized countries. Our objective is to establish the proof-of-concept that among a series of hit molecules identified by screening of new marine compounds, for their capacity to induce expression of AMP genes, a small subgroup may qualify to lead molecules that can then be pushed into the late phases of the R&D pipeline, with the perspective of a phase I clinical trial. To achieve this transition, our project will focus on the human intestinal mucosa as target. Screening specifications for a molecule to qualify as a hit require that they induce strong expression of AMP genes, without triggering expression of pro-inflammatory genes, which could be deleterious for the mucosa. The novelty of this technology resides in looking for molecules that act as inducers of host AMP gene expression, by targeting (epi)genetic regulatory functions, reducing the risk of resistance in bacteria. Our project ranges from the understanding of (epi)genetic mechanisms regulating AMP gene expression, to the identification of new natural molecules inducing their expression, the optimization of molecules by medicinal chemistry, their characterization and evaluation of their protective efficacy in pre-clinical validation models. Ultimately, we expect to select molecules as future drug candidates, and to provide better understanding of the homeostasis of mucosal defenses, in line with the concept of (epi)genetic pharmacology.