The project “Stratified Medicine Algorithm for host-directed therapy in TuBerculosis” (SMA-TB, GA 847762) is one of the 10 projects funded by the programme Horizon 2020 of the European Commission in the area “prevention, treatment and cure of infectious diseases”. The team headed by Dr Jérôme Nigou at the IPBS-Toulouse1 is engaged in this project, which aims to elaborate a new therapeutic strategy to fight tuberculosis. The project has received a total funding of 6.3 million euros, with around 650 k€ attributed to our Institute, and will run for four and half years.
Tuberculosis, known as TB, is a disease caused by Mycobacterium tuberculosis bacteria that attack the lungs. It can persist throughout a person’s life or even kill the patient. The standard TB treatment is the same for all the patients and consists of antibiotics that are designed to kill the bacteria. SMA-TB is an international project led by the Germans Trias i Pujol Research Institute (IGTP) in Spain and will be carried out by eight institutions in France, Georgia, Germany, the Netherlands, Norway, South Africa and Spain. It will run a clinical trial to test the impact of aspirin as an adjunctive therapy to the standard antibiotic therapy used for TB treatment.Indeed, antibiotic therapy is very long, with many side effects, and its success depends on antibiotics availability and on the sensibility of the bacterial strains to these antibiotics. Resistant strains (MDR- and XDR-TB) are not killed by the common drugs and are much more difficult to eliminate, which makes the treatment much longer and more unpleasant for patients who can also be left with worse long-lasting, and sometimes life-long, effects. TB patients undergo lung damage. Those who are worst affected suffer from runaway lung inflammation, with damage that can remain even after they are cured.
“Host-directed treatments (HDTs) are a new type of complementary therapy aiming at boosting the patients’ own defences and ability to fight off disease. In the case of tuberculosis this is designed to complement the effect of the antibiotics, which only eliminate the infecting microorganisms but do nothing to reduce damage to the lungs” explains Cristina Vilaplana, researcher at the IGTP and CIBERES and coordinator of SMA-TB. If HDTs can be included in the medicines that the patients are already taking, this could reduce the inflammation, the length of the treatment, and the magnitude of lung damage.
To reach this goal, the SMA-TB project has 3 aims:
- It will run a high-quality clinical trial including patients in several countries, in which patients being treated for TB will also be given aspirin, to reduce inflammation. The trial will include patients whose TB is sensitive to the normal drug therapy and patients whose TB is resistant to this treatment. The researchers expect to show that the use of aspirin allows a reduction of the treatment duration and the patients to suffer less lung damage.
- Part of the research will identify biomarkers that doctors can use to reliably stratify patients and predict who can be treated successfully by the standard treatment and who will need to complete the drug treatment with HDT. It will also study the prognosis and outcomes for patients in different groups. Data from very large numbers of patients will be collected and network-based mathematical modelling will be used to identify patterns in the data.
- Combining the information on stratifying patients and outcomes for different cases, the researchers will produce a medical algorithm to be applied to new patients. This should allow doctors to predict the course of the disease and to apply the best clinical management for each patient.
The team "Immunomodulation By Mycobacterial Lipids and Glycoconjugates" led by Jerome Nigou from the IPBS-Toulouse will play a key role on the identification of biomarkers from bacterial origin.