{"id":55245,"date":"2026-03-24T14:11:28","date_gmt":"2026-03-24T07:11:28","guid":{"rendered":"https:\/\/www.oucru.org\/?p=55245"},"modified":"2026-04-06T10:09:50","modified_gmt":"2026-04-06T03:09:50","slug":"new-5-million-award-to-transform-tbm-treatment","status":"publish","type":"post","link":"https:\/\/www.oucru.org\/id\/new-5-million-award-to-transform-tbm-treatment\/","title":{"rendered":"New \u00a35 million Wellcome Discovery Award to transform treatment for tuberculous meningitis"},"content":{"rendered":"

Tuberculous meningitis (TBM) is one of the most severe forms of tuberculosis, killing between 30 and 50% of those who develop it despite treatment. Doctors have relied on the same basic approach since the 1950s: antibiotics to kill the bacteria, and corticosteroids to reduce the dangerous brain inflammation that the infection causes.\u00a0\u00a0<\/p>\n

Recent\u00a0OUCRU\u00a0clinical trials, including\u00a0HARVEST<\/a> (NEJM Dec 2025); SURE<\/a> (unpublished); ACT HIV<\/a>\u00a0(NEJM Oct 2023);\u00a0LAST ACT<\/a>\u00a0(Nat Med Jan 2026),\u00a0have shown that this approach is not good enough: higher-dose antibiotic regimens have worsened outcomes rather than improved them, and corticosteroids appear\u00a0not to control\u00a0inflammation or\u00a0benefit\u00a0most patients.\u00a0The field needs a new direction.\u00a0<\/p>\n

The opportunity\u00a0<\/h4>\n

There are real opportunities to improve TBM treatment. A resurgent pipeline of new anti-tuberculosis drugs may kill bacteria faster than current drugs, and targeted anti-inflammatory drugs may control life-threatening brain inflammation better than the corticosteroids used as standard of care today.\u00a0<\/p>\n

However, these opportunities are impaired by three critical gaps: a poor understanding of disease and therapeutic mechanisms; a lack of animal models that can predict whether new drugs and regimens will work in humans; and no reliable biomarkers to measure whether treatment is succeeding.\u00a0<\/p>\n

A major new research\u00a0programme, funded by a \u00a35 million\u00a0Wellcome\u00a0Discovery Award<\/a>\u00a0over five years, will seek to close those gaps. Led by\u00a0Professor Guy Thwaites<\/a>\u00a0at\u00a0the\u00a0University of Oxford<\/a>, the project brings together an international team from\u00a0OUCRU\u00a0Vietnam<\/a>,\u00a0CIDRI-Africa<\/a>\u00a0in Cape Town,\u00a0South Africa, the UK, and the USA. The\u00a0programme\u00a0will start in October\u00a02026.\u00a0<\/p>\n

\u2018This is an incredibly exciting time in tuberculosis, with new anti-tuberculosis and anti-inflammatory drugs becoming available to\u00a0improve treatment. But unless we understand the\u00a0fundamental relationship between\u00a0bacterial killing, inflammation, and outcome, we risk using the\u00a0new\u00a0drugs wrongly and missing the\u00a0opportunity\u00a0to increase\u00a0survival from this lethal disease,\u2019\u00a0said Professor Guy Thwaites.\u00a0\u00a0<\/p>\n

What the\u00a0research\u00a0will do\u00a0<\/h4>\n

The team will create a platform for the pre-clinical and clinical discovery and development of new therapeutic strategies for TBM, linking human experimental medicine in Vietnam and South Africa with animal models in the USA.\u00a0<\/p>\n

In the human study, the team will\u00a0test four treatments in 160 adults with TBM:\u00a0two potent bedaquiline-containing anti-tuberculosis regimens,\u00a0and two drugs that target inflammation in the brain rather than the bacteria themselves. The study aims to quantify the relationship between drug concentrations in the body, bacterial killing, inflammation, and clinical outcome,\u00a0and to discover novel inflammatory and physiological biomarkers that could be used to measure treatment success in future trials.\u00a0<\/p>\n

In parallel, the team will use rabbit and mouse models of TBM to define how well animal studies can predict human therapeutic responses. The models will also be used to evaluate the therapeutic potential of three new drugs in clinical development, ganfeborole (GSK<\/a>),\u00a0telacebec\u00a0(TB Alliance<\/a>), and TBAJ-876 (TB Alliance),\u00a0establishing\u00a0their role in the discovery and development of new treatment strategies for TBM.\u00a0<\/p>\n

An international team\u00a0<\/h4>\n
\"\"<\/a>
The research team spans Vietnam, South Africa, the United Kingdom, and the United States. Map: Guy Thwaites.<\/figcaption><\/figure>\n

The\u00a0research\u00a0is led by\u00a0Guy Thwaites, with\u00a0Sarah Walker<\/a> (University of Oxford), Nguy\u1ec5n\u00a0Th\u1ee5y\u00a0Th\u01b0\u01a1ng\u00a0Th\u01b0\u01a1ng<\/a> and\u00a0Joseph Donovan<\/a> (OUCRU Vietnam), and Martin Gengenbacher\u00a0<\/a>(Center for Discovery & Innovation, USA<\/a>).\u00a0The team also includes Robert\u00a0Wilkinson<\/a>,\u00a0Cari Stek<\/a>,\u00a0Sean\u00a0Wasserman<\/a>\u00a0and\u00a0Paolo Denti<\/a> at the\u00a0University of Cape Town<\/a> and CIDRI-Africa, South Africa.<\/p>\n

Industry collaborators include GSK, TB Alliance,\u00a0Medicines Development for Global Health<\/a>, and\u00a0BioVersys<\/a>.\u00a0<\/p>\n

Looking ahead\u00a0<\/h4>\n

TBM disproportionately affects people in low- and middle-income countries. New drugs are beginning to\u00a0emerge, but without the knowledge to deploy them safely and effectively, their potential may not be\u00a0realised.\u00a0\u00a0<\/p>\n

This\u00a0research\u00a0aims to provide that knowledge,\u00a0and in doing so, lay the foundation for a new generation of clinical trials that could meaningfully reduce deaths from this devastating disease.<\/p>\n","protected":false},"excerpt":{"rendered":"

The treatment for tuberculous meningitis has not changed since the 1950s. 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