Descrizione del progetto
Batteriofagi nel trattamento della tubercolosi
I batteriofagi sono virus che infettano e uccidono i batteri. La crescente minaccia della resistenza ai farmaci ha riacceso l’interesse verso questa opzione terapeutica. Finanziato dal programma di azioni Marie Skłodowska-Curie, il progetto Phage-TB mira a sviluppare trattamenti clinici con micobatteriofagi per la tubercolosi (TBC) e le infezioni da micobatteri non tubercolari. Il DNA dei micobatteriofagi isolati nel suolo sarà sequenziato per selezionare i candidati promettenti con effetti litici contro le infezioni da TBC o da micobatteri non tubercolari. I cocktail di fagi saranno ottimizzati per il metodo di inalazione nel trattamento clinico, preservando i fagi intatti e funzionali. Il cocktail di micobatteriofagi selezionati contro la tubercolosi sarà utilizzato nel primo studio clinico sull’uomo volto a valutare sicurezza, dosaggio ed efficacia.
Obiettivo
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.
Campo scientifico
Programma(i)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Meccanismo di finanziamento
HORIZON-TMA-MSCA-PF-GF - HORIZON TMA MSCA Postdoctoral Fellowships - Global FellowshipsCoordinatore
6525 GA Nijmegen
Paesi Bassi