Title: A novel Stratified Medicine Algorithm to predict treatment responses to host-directed therapy in TB

Link: https://www.smatb.eu/

Tuberculosis (TB) is a chronic, life-threatening infectious disease which poses a tremendous challenge for physicians, researchers, and Health Systems, which treatment is long, based only on the drug susceptibility of the responsible infective strain and very costly in drug-resistant cases (MDR-TB). The European Region still has the highest prevalence of MDR-TB in the world. Host-Directed Therapies (HDT) have been recently proposed to shorten treatment length and by to improve the patients’ outcomes while not increasing the risk of generating drug resistance. As hyperinflammation is responsible of the lung damage associated to patients’ worse outcomes and sequelae, one of the approaches is to add an HDT with anti-inflammatory effect to the current drug regimen to cure the patients faster while having less permanent lung damage. Because TB has a wide range of clinical forms and severity stages, any therapeutic regimen needs to be studied in clinical trials (CT) as its benefit might differ among patients. No individualized personalized medicine is possible without stratifying the patients by integrating pathogen and host factors that will predict the course of the disease and the response to the intervention. 

SMA-TB objectives are:

• To evaluate in a CT the potential impact of aspirin (an anti-inflammatory HDT) as adjunct to standard therapy for drug sensitive (DS-) and MDR-TB. This potentially will reduce tissue damage, decrease the length of the treatment and the risk of bad outcomes.
• To identify and clinically validate host and pathogen biomarkers for further selection according to their relevance in terms of their ability to predict TB course and outcomes and response to treatment thanks to data science protocol.
• To generate a medical algorithm to stratify patients using network-based mathematical modelling for predicting the course of the disease and its response to the intervention, to be applied during clinical management to improve and personalize TB.

 

Partner Institutions

FUNDACIÓ INSTITUT D’INVESTIGACIÓ EN CIÈNCIES DE LA SALUT GERMANS TRIAS I PUJOL

The Germans Trias i Pujol Research Institute (IGTP) is a public research centre in the Autonomous region of Catalonia in Northern Spain dedicated to increasing scientific knowledge and transferring it to improve the care and lives of patients. IGTP activities will be carried out by the Experimental Tuberculosis Unit. UTE’s expertise is:

• Development and evaluation of new prophylactic and therapeutic strategies against TB 
• Study of biomarkers in samples obtained in tuberculosis clinical studies and trials 
• Development and evaluation of new tools to improve diagnosis, management and quality of life of patients affected by TB
• Development of new experimental models (in vivo, in silico) in order to mimic better the human tuberculosis and its evolution, including mathematical approaches.

Key Personnel involved

Cris Vilaplana

Pere-Joan Cardona

Maria-Rosa Sarrias

Vanessa Llobet

Lilibeth Arias

Laura Villegas

WITS HEALTH CONSORTIUM

The Wits Health Consortium (Pty) Limited (WHC) is a non-profit organisation which started in 1998. Perinatal HIV Research Unit (PHRU) is a division of the WHC. PHRU performs high quality clinical research into aspects of the HIV and TB epidemics that could mitigate the impact of these pathogens on humanity. PHRU’s Soweto and Matlosana sites have recruited to multiple studies of novel TB agents – both drug sensitive and drug resistant. The sites have experience in recruiting patients with TB, consenting adults and children, and following up large cohorts of TB patients successfully.

Key Personnel involved

Neil Martinson

Tumelo Moloantoa

Ziyaad Waja

Ebrahim Variava

Limakatso Lebina

NATIONAL CENTER FOR TUBERCULOSIS AND LUNG DISEASES

NCTLD was founded in 2001 after reorganization, based on the Institute of Tuberculosis and Lung diseases, the city TB Hospital, and the Georgian Railway TB-Stationary. NCTLD historically has been recognized as a Center of excellence for specialized TB services and consists from several departments. Services provided include diagnosis and treatment of all forms of Tuberculosis, diagnosis and treatment of other pulmonary pathologies and surgery for TB patients. NCTLD also holds a clinical committee to support M/XDR-TB case management throughout the country.

Key Personnel involved

Sergo Vashakidze

Nestani Tukvadze

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

The Centre National de la Recherche Scientifique (CNRS) is the largest fundamental research agency in Europe. The Institute of Pharmacology and Structural Biology (IPBS) is a joint unit between the CNRS and the University of Toulouse, which benefits from a highly collaborative and innovative scientific environment with access to state-of-the-art technological facilities in-house and on the Toulouse University scientific campus.

The main focus of the Nigou lab, Immunomodulation by Mycobacterial Lipids & Glycoconjugates, is to decipher the molecular cross-talk that establishes between M. tuberculosis and host immune cells during infection. Besides providing new knowledge with regards to host-pathogen interaction, it aims at translating these fundamental data into potential new therapeutic or preventive strategies/tools.

Key Personnel involved

Jérôme Nigou

Emilie Layre

ACADEMISCH ZIEKENHUIS LEIDEN

LUMC is a university medical center for research, education and patient care with a high quality profile and a strong scientific orientation. The LUMC Infectious Diseases (LUMC-ID) group has established an internationally well recognized and competitive research program in the field of human immunology, cell biology and immunogenetics of mycobacterial infectious diseases. The mission of LUMC-ID is to dissect immunological and host-genetic mechanisms of protective and pathologic immunity to mycobacterial infections and related infectious diseases, to design more effective intervention strategies.

Key Personnel involved

Tom H.M. Ottenhoff

Mariëlle C. Haks

OSLO UNIVERSITETSSYKEHUS

Oslo Universitetssykehus HF (OUS) (Oslo University Hospital, OUH) is a highly specialized hospital in charge of national, regional and local hospital assignments with regional responsibilities for MDR/XDR-TB. The Chronic Infections Research Group (CIRG) at Department of Infectious Diseases, OUS, has been the sponsor for several phase I/II clinical trials, performs prospective bio-banking of human TB samples with corresponding registration of clinical data in a TB register. CIRG focuses on translational research on immune mechanisms, diagnostics and host-directed therapy and holds a state-of-the-art immunological laboratory strategically integrated within the clinical ward with P3/P4 laboratory, including facilities for cell culture and analysis (flow cytometry and sorter, ELISA, BioRad multiplex and ELISPOT readers).

Key Personnel involved

Anne Margarita Dyrhol-Riise

ANAXOMICS BIOTECH S.L.

Anaxomics is a company specialized in bioinformatics and systems biology providing services for drug discovery, pre-clinical and clinical development. Anaxomics proprietary technology based on systems biology builds mathematical models applying machine learning methods to infer clinical and protein level knowledge. The analysis of these models provides mechanistic insight into the understanding of the complexity of biological processes and innovative solutions to take our understanding of drugs and diseases to a new level.

Key Personnel involved

Judith Farrés

José Manuel Mas

Teresa Sardón

TES2A EUROPE CONSULTING AND BUSINESS DEVELOPMENT S.L. 

TES2A Europe is a Spanish SME, founded in 2010 and focused on consulting and business development, based on feasible results of research and development activities carried out by individual companies or international consortia. TES2A Europe has a wide range of range of expertise and extensive experience in giving support in European project co-coordination and partnering.

Key Personnel involved

Iwona Maciejewska

LIONEX GMBH

LIONEX Diagnostics & Therapeutics GmbH” (LIO). LIO is a German biotech company with exceptional commitment to the problems of cancer and tropical diseases such as TB and HIV. LIO has produced large quantities of endotoxin free, antigens of M. tuberculosis from E. coli. Also LIO has developed a novel test for diagnosing Latent TB Infection (LTBI)/TB.

Key Personnel involved

Mahavir Singh

Wulf Oehlmann

Ayssar Elamin

Fatima Jonas

Katja Truthmann