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Research on improvements in diagnosing and treating tuberculosis
21 June 2012
Universidad Carlos III de Madrid - Oficina de Información Científica
Scientists at the Carlos III University in Madrid (UC3M) are participating in a European research project designed to study tuberculosis treatments. The objective of the study is to improve diagnostic imaging technology in order to help develop new drugs to treat the disease.
Project PreDiCT-TB is being developed jointly by the Seventh Framework Program and the European pharmaceutical industry in the hopes of studying and improving the treatment of tuberculosis, and infectious disease that affects nearly nine million people throughout the world.
The goal is to develop a set of pre-clinical trials (‘in vitro’ and ‘in
vivo’) that will provide critical data for identifying decision-making criteria regarding the effectiveness of a given treatment, as well as to optimize the clinical studies of new combinations of drugs used to fight tuberculosis. “These data will, first, offer us an early evaluation of the efficiency of the combinations of drugs used to treat tuberculosis; and, second, they will allow us to optimize the clinical studies with patients”, states the head of research at UC3M, Juan José Vaquero, from the Bioengineering and Aerospace Engineering Department.
The work being done at this Madrid university is mainly focused on the research and the development of new pre-clinical imaging technology, as well as on methods for processing and analyzing images for the evaluation and follow-up of illness in animal models. “We are going to develop new in vivo molecular image devices and also work on the synthesis of very specific probes for the biomarkers of this illness that have been identified by other partners in the consortium”, explains Juan José Vaquero. “We are collaborating very closely with GlaxoSmithKline, whose laboratories are going to use our equipment, as well as with specialists from the Infectious Disease and Microbiology Service of Gregorio Marañon University General Hospital (Servicio de Enfermedades Infecciosas y Microbiología del Hospital General Universitario Gregorio Marañón - Madrid), who have a great deal of experience working with both the biology and the clinical aspects of tuberculosis; this facilitates the transformation of our results into clinical applications”, comments the professor.
UC3M is participating in this project as a technological partner. Its contribution is focused on its role as a specialist in pre-clinical molecular imaging in animal models. The short-term goal is to develop a low-cost tomographic X-ray technique for rapid screenings. With such a technique, the scientists could follow the evolution of the disease and evaluate the effectiveness of treatments in animal models. The long term goal is to perfect this technique, including positron emission tomography (PET) in order to make it more sensitive and specific, so that it can be used to take quantitative measurements. This procedure would substitute the one that is currently being carried out in the laboratory, which is slower and more costly. To complete this substitution, changes in the imaging technology will be introduced, so that greater resolution can be obtained. “This way–Vaquero explains- with just one examination, we will be able to visualize the complete lung of a rat or guinea pig, with enough detail to detect the disease at its earliest possible stage”.
This is the first time the use of quantitative molecular imaging is proposed to study the disease in animal models. It carries a technological and methodological challenge, because its development requires blending various research groups: new electronic radiation detection technologies are going to be used to improve the sensitivity of the current systems and, at the same time, algorithms for image reconstruction and quantitative analysis that accompany the new electronic technology are going to be applied.
A forgotten disease
This project is centered on the so-called “forgotten diseases” or “developing countries’ diseases”, specifically on tuberculosis. For the last thirty years there have been no new approaches to treating this pathology. Among infectious diseases, this is the main cause of death among young adults in developing countries, particularly among the poorest ones. It is estimated that there are five million new cases every year throughout the world and that the possibility of being cured is only 60%. The efficacy of programs to fight tuberculosis continues to be burdened by the need to keep patients in treatment for 6 to 24 months. Financing and support for trials are limited.
With its participation in this project, UC3M has joined large-scale research in the area of health science. The project, which began in May of this year and is expected to last for sixty months, is being led by the pharmaceutical company GlaxoSmithKline and includes 21 prestigious international partners. The partners who come from private industry
are: GlaxoSmithKline, Sanofi-Aventis, Janssen, Microsense Medtech and ZF Screens. Partners from the academic world are: the University of Liverpool, UC3M, Max Plank Institute, Erasmus University, Health Protection Agency UK, Institut Pasteur, St Georges University London, University of St Andrews, EPFL, Univ. of Leicester, University College of London, VU University, the Liverpool School of Tropical Medicine and Uppsala University.
This project is being carried out within the Innovative Medicines Initiative (IMI), collaboration among the EU, European pharmaceutical companies, regulators, academia and patients’ associations. The initiative’s main objectives are to give a new impulse to the European pharmaceutical industry and biopharmaceutical research, oriented toward the search for solutions to the scientific challenges presented by the search for new medications. The program is jointly financed by the EU and the members of the European Federation of Pharmaceutical Associations (EFPIA), with 50% of the research being funded by the EU and the remaining 50% contributed almost entirely by the three participating pharmaceutical companies. It is hoped that through the collaboration of all of these experts data and knowledge will be shared, in order to tackle the current challenges involved in research on pre-competitive medicines and in their development.
PET/CT scan images from a healthy guinea pig (left), and from an infected guinea pig with chronic pulmonary inflammation (right). The image of the lung that was acquired using tomography can be seen in black and white, while the image in color shows the most active areas as detected by the PET scan, which correspond to the active inflammatory process.
Preparation of the animal for the PET/CT tomography. The rat is connected to an anesthesia system and a vital signs monitor that insures its well-being during the entire imaging session. When the process is finished, the animal is returned to its cage.