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Improved therapies for soil-transmitted helminthiases: exploring pharmacomicrobiomics, novel drugs and microfluidic assay platforms

Description du projet

Vers la prochaine génération de médicaments contre les infections helminthiques

Les infections par des vers parasites représentent un fardeau considérable pour la santé publique, et les options de traitement sont limitées. Le projet DRUGSBUGS, financé par l’UE, entend améliorer la compréhension des principaux anthelminthiques actuels et de ceux à venir, en particulier la modulation du traitement anthelminthique en fonction du microbiome en raison de l’interaction entre les microbes intestinaux et les médicaments. En outre, les chercheurs jetteront les bases de la découverte et du développement de la prochaine génération d’anthelminthiques en testant l’émodepside dans des essais cliniques de phase 2a et 2b et en investissant dans de nouvelles technologies innovantes dans le domaine de la découverte de médicaments.

Objectif

An estimated 1.5 billion people are infected with soil-transmitted helminths (STHs) causing a global burden of 1.9 million disability-adjusted life years (DALYs). Current treatment options are limited. Preliminary studies in my lab hint towards a gut microbiome mechanism responsible for treatment failures of the most efficacious treatment currently available, albendazole-ivermectin. I propose an innovative 5-year project (“DRUGSBUGS”) that holds promise for major breakthroughs in anthelminthic drug discovery and development. I will deepen the understanding of current and potentially upcoming anthelminthics, in particular the microbiome-driven modulation of anthelminthic treatment. I will investigate underlying gut microbial structures in human stool samples associated with efficacy of albendazole-ivermectin treatment. Findings will be experimentally validated in vitro and in vivo. In addition, I speculate that emodepside will emerge as a novel key player in the anthelminthic drug armamentarium, which will enhance efficacy and reduce the risk of selection of resistant helminth populations. DRUGSBUGS proposes two Phase 2a dose selection trials with emodepside against Trichuris trichiura and hookworm in adults. Subsequent Phase 2b studies will assess whether emodepside is superior to albendazole against hookworm and T. trichiura. Using a microsampling technique, I will characterize the pharmacokinetics of emodepside in patients infected with T. trichiura and hookworm. In parallel, investing in innovative new technologies in the field of drug discovery will facilitate the discovery and development of the next generation of anthelminthics. I propose to study drug effects on motility and viability of different STH larvae applying electrical impedance spectroscopy on a microfluidic chip platform. My proposed research is of considerable public health relevance since it will ultimately result in improved treatments for soil-transmitted helminthiases.

Régime de financement

ERC-ADG - Advanced Grant

Institution d’accueil

SCHWEIZERISCHES TROPEN UND PUBLIC HEALTH INSTITUT
Contribution nette de l'UE
€ 2 470 621,00
Adresse
KREUZSTRASSE 2
4123 Allschwil
Suisse

Voir sur la carte

Région
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Landschaft
Type d’activité
Research Organisations
Liens
Coût total
€ 2 470 621,00

Bénéficiaires (1)