Two Inserm-led projects have been recognized by the 2018 Europe's Rising Stars awards [Étoiles de l'Europe]. This prize is awarded by the Ministry of Higher Education, Research and Innovation for high-quality projects, led by French teams involved in a European network, with a multidisciplinary approach. The two Inserm prize-winners are FIBRO-TARGETS, a project aiming to fight against heart failure, and REACTION, dedicated to developing a treatment for Ebola.
Created in 2013, Europe's Rising Stars award recognizes coordinators of research and innovation projects supported by a French organization, who "choose Europe". These Rising Stars, originating from diverse sectors (universities, organizations, schools, and business), are selected based on the scientific quality and international scope of their projects, along with their economic, technological and community impact, and the multidisciplinary dimension of their projects.
Since 2014, the FIBRO-TARGETS project has brought together eleven multidisciplinary European teams - including small and medium-sized enterprises - on the theme of heart failure. Professor Faiez Zannad, Cardiologist and Director of the Nancy clinical investigation center*, coordinated this project, which benefited from EUR 6 million in European Union funding. The objective was to study the mechanisms of heart tissue fibrosis, involved in the onset and progression of heart failure. The consortium then went on to investigate new therapeutic targets, to curb the progression of this disease, the main cause of hospital admissions among over 65 year-olds. "Fibrosis is systematically associated with heart failure. It often even appears before the disease itself. An effective, targeted approach to fighting this phenomenon would most certainly reduce the burden related to this type of heart disease, or indeed slow its development in subjects at risk: hypertensive, elderly or diabetic patients," clarifies Faiez Zannad.
Each team concentrated on their own area of expertise – in vitro on molecular models and in vivo on different animal models - so as to validate the reality of four fibrosis mechanisms investigated, and identify therapeutic targets. These include cardiotrophin, galectin-3, lipocalin, apelin, and microRNA. Molecular screening was then carried out on these targets, with a view to identifying candidate drugs able to block their activity. Approximately ten candidates have already been tested in the preclinical phase, and patented. Some are even expected to enter initial clinical trials in the very near future.
This research has already been reported in numerous scientific publications. The 2018 Europe’s Rising Stars award consistently offers projects greater visibility so as to pursue this colossal undertaking.
The REACTION project was initiated back in 2014, in response to the Ebola epidemic in Guinea, under the impetus of Inserm and the Aviesan partnership Immunology, Inflammation, Infectiology and Microbiology Theme-Based Institute. In the context of this major health crisis, the project involved evaluating the efficacy and safety-in-use of favipiravir, an antiviral agent developed for the influenza virus, which had demonstrated a certain degree of efficacy against the Ebola virus in a rodent model.
A consortium bringing together French and European scientists was formed with a view to implementing this vast project comprising a phase 2 clinical trial in the field (JIKI trial) and preclinical trials. "This project was ground-breaking owing to its urgent context faced with an uncontrollable, deadly disease, in a rural region culturally different to Europe, with failing health facilities. Its creation and implementation required unparalleled proactivity and cohesion between numerous partners and experts who rarely work together: clinicians, biostatisticians, academic researchers from extremely diverse fields, and even anthropologists one of whose tasks was to obtain informed consent from patients in Forested Guinea," explains Professor Hervé Raoul, Director of the BSL-4 Laboratory at Inserm Jean Merieux* in Lyon, in charge of the project.
This professionalism and state of affairs convinced the European Commission to rapidly release funding as part of the Horizon 2020 program. Favipavir was thus able to be tested in more than 100 patients, at equivalent doses to those used to treat influenza. The results did not evidence any significant efficacy in terms of survival rate, relative to untreated patients. However, collection of biological specimens shed more light on the behavior of the infectious agent and response to treatment. At the same time, the consortium conducted preclinical trials in non-human primates, to test other doses. This approach showed that the medicinal product could be effective at a higher dose, although this still needs to be confirmed in humans, if a new epidemic were to break out.
Approximately 25 articles have been published further to this body of research. "We are now convinced of the benefit of this agent in the armamentarium against Ebola, in combination with other treatments," concludes Hervé Raoul.
*CIC 1433 Inserm/Lorraine University/Nancy University Hospital
**Inserm Service Unit 3