Mtb has acquired a remarkable ability to exploit cellular host factors for its own survival and persistence. Targeting these factors could thus become promising candidates for adjunctive host-directed drug therapeutics to reduce tissue pathology, Mtb burden, TB relapse and potentially shortening duration of current anti-TB treatments.
Mtb establishes its infection by targeting macrophages primarily in the lung. Active TB patients contain characteristic foamy macrophages in their lung where intracellular host cholesterol ester is accumulated, a major component of lipid droplets. Therefore, the bacterium needs to be able to use cholesterol from the host in order to maintain a chronic infection.
Cholesterol is lowered by statins, which are currently prescribed and licensed globally and have made a significant beneficial impact in patients for reducing the risk and mortality of cardiovascular diseases. However, statins are currently not prescribed anywhere in the world for the treatment of TB.
StatinTB introduces statins as an adjunctive therapy for TB patients, by re-purposing a drug as a low risk and cost-effective method to lower TB relapse and significantly reduce post-TB chronic lung disease.
Unlike the conventional TB treatment with antibiotics, statins act directly on host cell functions, thus avoiding the development of TB drug resistance.
Statins could therefore become a promising treatment strategy to increase the host antimicrobial responses and to limit chronic inflammation and pulmonary tissue damage. Moreover, the impact on drug development, lead-time to market and future practical implementation for the use of statins as HDT for TB could be fast tracked because statins are already EMA/FDA/MCC approved for the treatment of cardiovascular diseases.
The consortium hypothesizes significant improvement after treatment with statins, which will lead to a much higher quality of life by improving lung health, allowing patients to return to a healthy state after the end of their TB treatment.
The outcomes of the project will positively impact the lives of TB patients as follows:
1) Patients will benefit from a reduced probability of TB relapse. This means that fewer patients will have to cope with the devastating news of the disease coming back following completion of their treatment, and that subsequent treatment cycles can be avoided.
2) As acquired drug resistance is particularly common among relapse patients, fewer relapse cases will also help reduce the development and spread of drug resistant TB.
3) Lastly, after successful completion of their TB treatment, patients will be significantly less likely to develop chronic lung disease, which will lead to a much higher quality of life.