Description du projet
Les bactériophages dans le traitement de la tuberculose
Les bactériophages sont des virus qui infectent et tuent les bactéries. La menace croissante que constitue la résistance aux médicaments a ressuscité l’intérêt pour cette option thérapeutique. Financé par le programme Actions Marie Skłodowska-Curie, le projet Phage-TB vise à développer des traitements cliniques par mycobactériophages (MBP) contre la tuberculose (TB) et les infections à mycobactéries non tuberculeuses (MNT). L’ADN des MBP isolés par le sol sera séquencé afin de sélectionner les candidats prometteurs ayant des effets lytiques contre les infections par TB ou MNT. Les cocktails de phages seront optimisés pour la méthode d’inhalation dans le traitement clinique, en gardant les phages intacts et fonctionnels. Le cocktail de MBP choisi pour lutter contre la tuberculose sera utilisé dans la première étude clinique chez l’homme afin d’en évaluer l’innocuité, le dosage et l’efficacité.
Objectif
The emergence of drug-resistance to tuberculosis (TB) drugs poses an increasing challenge to TB control and new treatment options are urgently needed. Novel or repurposed antibiotics are still being introduced, but this pipeline will dry out in the near future.
Bacteriophages are viruses that kill bacteria. They have been used to treat infections before the introduction of antibiotics. With the emergence of drug-resistance there is renewed interest in this ancient treatment option. Clinical use of mycobacteriophages to treat TB and non-tuberculous mycobacterial (NTM) infections is still in its infancy.
This project contributes to 3 areas in the development of clinically useful mycobacteriophage treatments for TB and NTM infections:
- Phage discovery: From soil samples collected in the compounds of TB clinics and hospitals in Cape Town, South Africa, we will isolate mycobacteriophages using spot tests and plaque assays. DNA of newly discovered mycobacteriophages will be sequenced and during the return phase of this project I will select promising mycobacteriophages with lytic effect against TB or NTM infections, that can be used for development of phage cocktails for clinical use.
- Phage inhalation method: the efficiency of phage treatment is dependent upon the phage concentration reached at the site of disease. Phages that can attack M tuberculosis have long tails which might be vulnerable to manipulation. We will optimize an inhalation method leaving the phages intact and functional.
- Preparation for a clinical trial: an existing mycobacteriophage cocktail active against TB will be used for a first clinical study in humans to assess dosing, safety and efficiency.
If our mycobacteriophage hunt is successful, and the translation can be made into purified and adequately dosed administration of mycobacteriophages, a virtually inexhaustible addition will be made to the therapeutic armamentarium for drug-resistant as well as drug-sensitive TB and NTM infections.
Champ scientifique
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
HORIZON-TMA-MSCA-PF-GF - HORIZON TMA MSCA Postdoctoral Fellowships - Global FellowshipsCoordinateur
6525 GA Nijmegen
Pays-Bas