Identification of biomarkers and new therapeutic targets in HTLV-1-associated pathologies.

Human T Lymphotropic Virus-1 (HTLV-1) was discovered 20 years ago as the first retrovirus associated to human cancer. In 3 to 5% of infected individuals, the virus causes adult T cell leukaemia/lymphoma (ATL), an aggressive form of leukaemia, characterised by resistance to chemotherapy and very poor prognosis (median survival time for the acute form: 6 months). Another 3 to 5% may develop HTLV I associated myelopathy (HAM), also known as tropical spastic paraparesis (TSP), a progressive neurodegenerative disease, leading to gradual paralysis and, eventually, death. In two decades, very little progress has been made in prevention of infection, clinical management or understanding of HTLV-1-associated pathogenesis. Our goal is to obtain new insight into HTLV-1-associated pathogenesis, in a stepwise manner. First, we will collect and manage epidemiologicic, clinical, virological and immunological HTLV-1 patient data (obtained through our collaboration with Brazil) in a database system and improve the system for clinical and research purposes. Second, we will identify cellular and molecular biomarkers for HTLV-1-associated pathologies through flow cytometry, immunogenetics and micro-arrays. Third, we will develop clinically useful algoritms by combining epidemiological, clinical and molecular data (in vitro and ex vivo) through datamining and modeling. Finally, we will try to characterize new therapeutic targets, against which novel small molecule compounds will be selected in our recently developed assay.

Keywords:Retrovirus, Pharmacogenomics, Data mining, Brazil, Spastic paraparesis, HTLV-1, Human T-lymphotropic virus, Therapeutic targets, Therapy, Biomarkers, Clinical virology

Disciplines:Scientific computing, Bioinformatics and computational biology, Public health care, Public health services, Immunology, Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences