New active agent for the treatment of tuberculosis

A recent clinical study shows that ganfeborole could be a promising candidate for the safe and effective treatment of pulmonary tuberculosis. Using microbiological testing and innovative imaging techniques, an international research team including DZIF scientists at the German Research Center Borstel - Leibniz Lung Center was able to prove the efficacy of this novel agent and pave the way for further clinical trials. The results have now been published in the renowned journal Nature Medicine.

The increase in drug resistance is making the treatment of tuberculosis, the most common fatal bacterial infectious disease worldwide, even more difficult. According to the World Health Organization (WHO), only 60 per cent of patients with multidrug-resistant tuberculosis are successfully treated worldwide. In recent years, strains of tuberculosis that are resistant to all available drugs have also become increasingly common. New drugs are therefore urgently needed.

Before new candidate drugs can be approved for the treatment of tuberculosis patients, they must undergo a series of development phases in clinical trials. An important step is the documentation of the so-called early bactericidal activity (EBA), in which the efficacy of a drug candidate is tested on tuberculosis patients in a 14-day monotherapy. If a drug shows sufficient early bactericidal activity, it is tested in more extensive clinical trials to investigate its efficacy, safety and effectiveness in the treatment of patients.

The Clinical Tuberculosis Unit (ClinTB) of the German Center for Infection Research (DZIF) at the Research Center Borstel, Leibniz Lung Center has been involved in conducting EBA studies for 10 years as a partner. Together with international colleagues, the researchers have now been able to show that the novel active substance ganfeborole exhibits clinical activity in patients. Ganfeborole belongs to a new class of antibiotics, the so-called "leucyl-tRNA synthetase inhibitors", which prevent the formation of new important proteins in bacteria and thus inhibit the growth of pathogens.

In addition to microbiological investigations into the effectiveness of Ganfeborol on the growth of tuberculosis bacteria, this study was the first to compare innovative imaging methods, so-called PET/CTs. With this method, which has been used successfully in tumor diagnostics, even minimal inflammation and cell changes caused by the bacteria can be made visible. 

The results of the PET/CTs were compared with extensive molecular biological investigations of RNA copies of the tuberculosis patients’ genetic material in their blood. "Using RNA analysis, we discovered an association between the activity of a certain cell population in the human body and the dosage of Ganfeboron. This correlation is also found in the PET/CT analysis data. Our results explain how changes in the imaging of pneumonia in tuberculosis are caused by the influence of drugs on metabolic activity," says Maja Reimann from the DZIF Clinical Tuberculosis Unit in Borstel. The method used here enabled the effectiveness of the drug on the lung tissue to be visualized at an early stage and could in future be an important tool in the clinical testing of new active substances and in the development of biomarkers.

The efficacy and tolerability of Ganfeborol will now be investigated in the next stage of clinical trials. In the PARADIGM4TB study, in which the Borstel DZIF team is participating, patients in Asia, Europe, Africa and South America are receiving Ganfeborol in combination with other antibiotics in order to determine the best combination for treating tuberculosis.

About the Research Center Borstel - Leibniz Lung Center

The Research Center Borstel is the lung research centre of the Leibniz Association. The centre focuses on chronic inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and allergies, as well as tuberculosis and other infection-related inflammations of the lungs. The overarching aim of the interdisciplinary research activities is to clarify the causes and mechanisms of chronic inflammatory and degenerative lung diseases in order to derive new innovative concepts for their diagnosis, prevention and treatment. The Research Center Borstel - Leibniz Lung Center is a member institution of the German Center of Infectious Diseases (DZIF).

Source: Press release of the Research Center Borstel - Leibniz Lung Center

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