CONFERÊNCIA “New drugs for Chagas disease treatment: From basic science to clinical trials” Julio A. Urbina1
1Venezuelan Institute for Scientific Research
Chagas disease, a systemic parasitosis caused by the Kinetoplastid protozoon Trypanosoma cruzi, remains the largest parasitic disease burden in the American continent and is now spreading to non-endemic areas due to intra and international migrations. Specific chemotherapy and treatment coverage of this condition are unsatisfactory due to the toxicity and limited efficacy of currently available drugs (nifurtimox and benznidazole), as well as controversies on the relevance of specific treatment in chronic patients. Recent studies have concluded, in contrast to long-held views on the autoimmune origin of the pathological manifestations of the chronic stage of the disease, that the persistence of parasites is the key factor underlying the sustained inflammatory responses that lead to these characteristic lesions. As a consequence, there is growing consensus that this condition should be treated as an infectious, not autoimmune, disease and that specific treatment should be offered to all seropositive patients, independently of the stage of the disease. Currently, the most promising approaches to new anti-T. cruzi drugs are: (a) ergosterol biosynthesis inhibitors (EBI), particularly novel triazole derivatives acting on the parasite’s CYP51 (sterol C14〈-demethylase) such as posaconazole and E-1224, a pro-drug of ravuconazole, which are currently undergoing Phase 2, poof-of-concept, clinical trials in Latin America and Spain, (b) amiodarone, an antiarrhythmic drug recently shown to have also potent anti-T. cruzi activity and to act synergistically with CYP51 inhibitors, (c) inhibitors of cruzipain, the main cysteine protease of T. cruzi, (d) EBIs acting on squalene synthase and (e) combination therapies such as benznidazole, nifurtimox or amiodarone associated with EBIs or combinations of EBIs acting at different steps of the pathway. Finally, a major stumbling block for the evaluation of new drugs, or the true efficacy of currently available drugs, is the lack of validated biomarkers of response to antiparasitic drugs and parasitological cure in chronically infected individuals. To address this issue several novel approaches are being advanced, including qualitative and quantitative PCR, specific biomarkers of cardiac compromise, hypercoagulability biomarkers, non- conventional serology and specific anti-T. cruzi T cell responses.
Julio A. Urbina, Ph.D.
Urbina recibió el titulo de Licenciado en biofísica de la Universidad Central de Venezuela (UCV, Caracas, Venezuela) in 1970 y de Ph.D. en química del Massachusetts Institute of Technology (Cambridge, Massachusetts, EUA) en 1975. De 1975 a 2006 se desempeño como Profesor de Biofísica y Fisicoquímica en la UCV y entre 1991 y 2005 fue también jefe del Laboratorio de Química Biológica del Instituto Venezolano de Investigaciones Científicas (IVIC, Caracas, Venezuela). En 1997 fue nombrado Fellow de la John Simon Guggenheim Foundation (New York, EUA), en 1997 recibió el premio Lorenzo Mendoza Fleury Prize en Ciencias Básicas de la Fundación Polar (Caracas, Venezuela), y de 2000 a 2005 fue Académico Internacional del Howard Hughes Medical Institute (Maryland, EUA). Urbina ha investigado durante mas de 35 años la bioquímica y fisiología de protozoarios patógenos y hongos, con el objetivo estratégico de desarrollar nuevos tratamientos específicos para las enfermedades causadas por esos organismos. Ha publicado 148 artículos en esa área, en revistas y libros arbitrados internacionalmente. Se desempeño en dos oportunidades (1981-1984, 1994-1999) como miembro del Consejo Superior del Consejo Nacional de Investigaciones Científicas (CONICIT) de Venezuela y ha sido asesor de la Organización Mundial de la Salud (OMS) y la Organización Panamericana de la Salud (OPS), así como miembro y Presidente del Consejo Científico Asesor de la Drugs for Neglected Diseases initiative (DNDi). Ha sido Profesor Visitante de numerosas universidades en Venezuela, Brasil, Argentina, Uruguay, España y Japón y actualmente es asesor científico de varias instituciones académicas y consultor de empresas farmacéuticas internacionales.
Accessible Websites for People with Dementia: a Preliminary Investigation into Information Architecture Centre for HCI Design, City University, London. People with dementia have not traditionally been seen as a user group for website development. This paper describes the first attempts to discover some of navigation design needs when developing an information-based website for people wit
ADRIANO CANZIAN – Bio EN ADRIANO CANZIAN studied sculpture and graphics, and then painting and contemporary art at Accademia delle Belle Arti in Rome, the city where he moved at 19. In 1995, he began exhibiting his work at various art galleries in Rome, London, Paris and New York. In the meantime, he moved to Paris in 2000 and started a parallel career as a music producer, working with t
CONFERÊNCIA 
Julio A. Urbina, Ph.D.