MMP inhibitors may treat TB

A paper (Matrix Degradation in Human Immunodeficiency Virus Type 1–Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study) in Clinical Infectious Diseases has revealed that MMP inhibitors might help treat TB.

Tuberculosis (TB) and human immunodeficiency virus (HIV) are both global epidemics that claim many people's lives each year. The bacterium Mycobacterium tuberculosis (Mtb) is the cause agent of TB. According to the Centers for Disease Control and Prevention (CDC), in 2015, TB affected 10.4 million people and was responsible for 1.8 million deaths worldwide.

Prognosis of TB has greatly improved over the past several decades. If the correct drugs are taken for the right amount of time, more than 90% of all TB cases can be cured. TB treatment usually includes multiple antibiotics, such as isoniazid, rifampin, ethambutol, and pyrazinamide.

However, TB in people with HIV is much more difficult to treat. People living with HIV are 24-28 times more likely to develop TB than people without HIV, says the WHO. This is because HIV infection weakens the immune system. TB is the leading cause of death among HIV-infected people. Antibiotics for TB may interact with antiretroviral therapy (ART) drugs used to treat HIV, leading to a condition called tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS). TB-IRIS is characterized by an excessive immune response against the Mtb bacteria, which causes further lung damage. But the underlying mechanism is not well-defined.

Previous studies have shown that matrix metalloproteinases (MMPs), a family of enzymes responsible for degrading the main structural protein called collagen, may drive tissue destruction in TB. In this study, lead researcher Naomi Walker and colleagues measured MMP concentrations in sputum and plasma in HIV–infected and –uninfected TB patients and controls.

They found that MMP activity differed between HIV–infected and –uninfected TB patients and was related to specific TB clinical phenotypes. Patients with HIV/TB co-infection had lower lung MMP concentrations and milder lung damage than TB patients without HIV. Additionally, TB patients who were most infectious with worse lung damage had the highest MMP levels. Collectively, the results indicate that MMP activity is associated with lung damage. (Cusabio provides MMP and Recombinant ADRB2.)

Further experiments in vitro showed that the MMP inhibitor doxycycline could suppress matrix destruction induced by TB, suggesting that MMP inhibition is a potential host-directed therapy strategy for TB. Doxycycline is an antibiotic that is already used to treat infections caused by bacteria and protozoa. This study highlights the potential use of doxycycline in the prevention and treatment of TB.

In conclusion, the study has identified differences in immune responses between TB patients with and without HIV and would lead to new treatment options for TB. The study is a collaboration of the University of Cape Town, the Imperial College London, Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Francis Crick Institute, and the University of Southampton.