Developing leads to shorten duration of TB chemotherapy: SHORTEN-TB

Shortening treatment times for patients with tuberculosis (TB) to prevent the development of drug-resistant TB strains

The Problem
The current standard of care for TB requires multiple drugs taken over a minimum of 6 months-noncompliance by patients during treatment can lead to drug resistance and exacerbate threats from multi-drug-resistant forms of TB.
The Solution
This project aims to identify new drugs against TB that shorten treatment times, which could increase the number of patients with drug-sensitive TB who complete treatment and thus help prevent multi-drug-resistant forms of TB.

Overview

Developing Lead Compounds to Shorten the duration of Tuberculosis Chemotherapy (SHORTEN-TB) is an effort to build upon lessons learned from the previous HIT-TB program and other recent advances in understanding how rate-determining steps that direct drug concentrations in TB lesions dictate the treatment-shortening potential of individual series as early as possible. The quality of leads will be assessed by measuring medicinal chemistry tractability, target novelty, ability to kill Mtb residing in caseum from granulomas and ability to be transported across lung alveolar cells. The project will advance hit series that the HIT-TB program predicted possessed characteristics needed to shorten the duration of chemotherapy, based on clinical evidence (oxazolidinones) or mechanistic novelty, where the engaged targets are predicted to play critical roles in the development of human TB pathogenesis. The program also continued screening libraries as collections with novel chemical diversity became available.

Partners

Public-Sector Partners

  • Helmholtz-Zentrum für Infektionsforschung GmbH (HZI)
  • National Institute of Allergy and Infectious Diseases (NIAID)

Private-Sector Partners

  • Bill & Melinda Gates Foundation*

Academic Partners

  • University of Cambridge
  • University of Cape Town
  • University of Dundee

*Provided financial or in-kind support for this program.

 

FNIH Contact

Goal

  • Identify new promising bacterial drug candidates (leads) and drug candidates to shorten the duration of TB drug therapy for all TB patients.