Our project aims at overcoming the elasticity defects of the arteries which are due either to genetic modifications or to ageing. To do this, a molecule was created in our laboratory and patented.
As with all pharmacological compounds for therapeutic purposes in humans, the safety and efficacy of our molecule must be validated beforehand on several animal models through preclinical research (Link 1 and link 2 below, link 2 is in French version only).
Research using animal models is regulated at the legislative and regulatory levels. European and French texts have been subject to regular revisions with an increasing consideration of animal welfare and European regulations are today the strictest at international level, in terms of protection of laboratory animals. (Link 3 below, French version only).
As with all research projects involving the use of animals, our projects are critically evaluated by an independent ethics committee made up of scientists but also at least one veterinarian and one person called “naive” (without scientific training) which will allow you to better anticipate questions from the population). The ethics committee then issues an opinion which is transmitted by the user establishment to the Ministry of Higher Education, Research and Innovation. The latter again evaluates the project and must validate it before any experimentation begins and this for a defined period.
For each project, it is fundamental to implement the “3Rs rule”:
Reduction: the number of animals must be reduced to a minimum without compromising the statistical interpretation of the results.
Refinement: animal welfare is a priority and all animal suffering must be reduced to a minimum throughout the life of the animal by setting up an adapted monitoring system, by defining sufficiently predictive and precise endpoints and by using medication adapted to the potential suffering that the animal could undergo.
Replacement: Animal research is only lawful if it “is of a strictly necessary nature”. Therefore, whenever possible, the use of alternative methods to the use of animals should be favoured.
Thus, several tests in silico (computer modelling) and in vitro were carried out and are included in our study to define the behaviour of our molecule in a simplified environment.
For this project, we have chosen to work on 2 animal species: the zebrafish and the mouse.
The zebrafish is a model animal which is relatively distant from humans but which shares 70% of its genome with us. In addition, tens of thousands of mutant fish have been generated around the world and in particular, fish with defects in the elastin gene, our gene of interest, which makes it possible to reproduce human pathology in this model and to observe the effect of our synthetic molecule in an entire organism. Finally, zebrafish, at very early stages of development, make it possible to quickly and effectively test the toxicity of pharmacological compounds.
The mouse is much closer to humans; we share 95% of our genes with the mouse. The transgenic mice we use reproduce the physiological characteristics of elastin deficient patients. This model is more complex to handle, but it allows us to better anticipate the behaviour of our compound in humans.
For more information, you can consult the links to the INSERM website :