The TOLLerant project aimed to address the medical and societal need of new anti-inflammatory drugs against infectious and non-infectious inflammatory diseases. New therapeutic approaches have been explored, based on the use of small-molecular TLR4 modulators, whose production could be scaled to an industrial level. This goal was achieved during the four years of project by the cooperative effort of a multidisciplinary consortium composed of 13 early stage researchers recruited by 8 teams from universities and 2 from companies located in different countries (Italy, Spain, Slovenia, Germany and Belgium).
Conclusions of the action:
The short term scientific objective of the project has been the study of molecular aspects of TLR4 activation and inhibition by using selective agonists and antagonists obtained by chemical synthesis or extracted from natural sources. This objective has been realized. Several New Chemical Entities (NCAs) were synthesized and delivered during the project (new synthetic molecules, new LPS variants from bacteria, nanoparticles functionalized with molecules). Some TLR4 antagonists were patented. The activity of these NCAs on TLR4 has been validated in vitro (binding experiments, microscopy, and experiments on human and murine cells) and in vivo in animal models of sepsis and LPS-induced pneumonia.
The NCAs produced in a collaborative way within the TOLLerant consortium are an important hit for drug development in the field of anti-inflammatory drugs, vaccine adjuvants, and substances for tumor immunotherapy. The delivery of NCAs therefore partially meets the long-term scientific objective of TOLLerant (develop specific drug hits based on small molecules and nanoparticles targeting TLR4).
The educational objective of the project has been to train the 13 early stage researchers hired by the consortium, providing them with scientific knowledge and industrial skills. During the 4 years project, the two companies collaborated with the academic groups of the TOLLerant consortium with the main objective to train 13 young scientists as the future leaders of the field to work in a multidisciplinary environment and to develop specific scientific, industrial and soft skills.
The young ESRs have been the real driving force of the basic science developed during the project. Several new projects and new ideas derived from brainstorming among ESRs and PIs during the network meetings. ESRs also greatly contributed to the spreading of results in the scientific community and to the communication and dissemination activities directed to the general public and to the society.
