Grant for research into highly deadly variant of tuberculosis  NIH supports study into the pharmacological optimization of current treatment

Radboud university medical center has been granted funding by the American National Institutes of Health (NIH) for research into tuberculous meningitis, one of the deadliest variants of tuberculosis. Up to 40% of patients with this form of the disease die. The current treatment is far from optimal. With this grant, a project is initiated where researchers aim to improve the treatment of tuberculous meningitis. They will focus particularly on the efficacy of the most commonly used tuberculosis drug in the brain and central nervous system.

Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis. The disease claims over a million lives annually, especially in Africa and Asia. Thus, tuberculosis is the deadliest infectious disease worldwide. While tuberculosis in the lungs is most common, the bacterium can also settle in other parts of the body, such as joints, bones, lymph nodes, or the brain. When there is inflammation of the meninges due to the TB bacterium, it is referred to as tuberculous meningitis. 

Although tuberculous meningitis is relatively rare (1-5% of all TB cases), it results in a significant number of deaths, around 100,000 per year worldwide. A considerable portion of surviving patients experiences severe neurological impairments due to the disease. Tuberculous meningitis is treated with a combination of four antibiotics. The main antibiotic, rifampicin, does not penetrate the brain and central nervous system effectively. Currently, a large-scale (phase 3) study is ongoing in Uganda, South Africa, and Indonesia to investigate the effects of a higher dose of rifampicin.

However, this phase III study does not address all questions surrounding tuberculous meningitis. Therefore, the American National Institutes of Health NIH has awarded a grant of 2.75 million dollar to Radboud university medical center. With this grant, lead researcher Lindsey te Brake and her colleagues Rob Aarnoutse, Arjan van Laarhoven, and Elin Svensson will explore the pharmacological optimization of current treatment and the role of the blood-brain barrier in effective therapy. 

Te Brake stated, ‘We anticipate that this project will yield fundamental knowledge regarding the function of the blood-brain barrier during an infection. With a better understanding of this mechanism, we can enhance treatment and thus exert global influence on this deadly form of tuberculosis.’

This study is funded by the National Institute of Allergy and Infectious Diseases (NIH) under grant number R01AI177101. This grant is made possible in cooperation with Grant Support Office.