The Jérôme Lejeune Foundation has associated itself with the Manros Therapeutics laboratory for an ambitious project aiming at developing new drug candidates to treat the cognitive disorders present in people with Down Syndrome. Founded in 2007, ManRos is a project developed by experts in cell biology and organic chemistry. It is led by Dr Laurent Meijer and Pr. Hervé Galons who are taking the project through the third stage of its development: after fundamental research and the adjustments of the first drug candidates, they now need to carry out further research to prepare for possible clinical trials!
Studying the Kinases
The majority of what goes on on a physiological (division, cellular death, etc.) level in cells is controlled by phosphorylation. This reaction is essential to cellular activity: it consists in adding a phosphate group to a molecule.
The enzymes that catalyse this phosphate group are called the Kinases proteins. Biological research has managed to put into evidence very clearly that many human pathologies are characterised by an anomaly in phosphorylation, in general linked to an abnormal activation of one or several of the 518 kinases present in the human body. In order to compensate for this anomaly, the lead which consists in inhibiting these kinases is one of the most promising fields of medical research such as shown by the three independent Nobel prizes awarded to research on the subject in 1992, 2000, 2001.
The ManRos projet
Professor Hervé Galons was the man who brought ManRos into existence in 2007.
Backed by the CNRS until 2010, ManRos rapidly raised funds to hasten the preclinical development of this family of molecules. Several of them can now enter into the third stage of this process, i.e., the selection of the drug candidates that can be taken into regulatory preclinical assessment (toxicity test battery on animals) and then clinical (test on human beings). It is in order to accompany this third stage of the ManRos “Down Syndrome” programme that the Jérôme Lejeune Foundation is supporting the project of Laurent Meijer and Hervé Galons.
|Structure of the DYRK1A|
TRIAD (for trisomie 21 (French for Down Syndrome) and Alzheimer’s Disease, the relationship between them both having been, indeed, long established) is the result of over 10 years of research. A first fundamental stage (PHARMACEA project) had enabled researchers to come out with a selection of two “lead” candidates: leucetines, derived from a marine sponge, and a molecules, derived from an Asian plant. This latter molecule is probably the most selective DYRK1A inhibitor ever described.
However, the Kinase protein DYRKIA is primordial in Down Syndrome. Overexpressed in Down Syndome, its role in the expression of intellectual disorders has been put into evidence in mouse models for Down Syndrome. Furthermore, the chromosome 21 is a carrier of the genes DYRK1A and APP, two proteins which play an important part in the development of Alzheimer’s disease. Research shows that there are also involved in cognitive disorders in Down Syndrome.
The strong probability that the protein DYRK1A is also involved in the cognitive disorders related to Alzheimer’s Disease only increases the relationships between the two diseases and the interest for a combined research programme.
The interest of research aiming at developing a new drug candidate founded on the inhibition of the Kinases protein DYRK1A is therefore twofold. The project TRIAD is an innovative research project which opens a new fascinating pathway to the understanding and treatment of both these diseases.
Within this project, ManRos managed to federate groups which are world renowned in their own field of expertise. These teams have been collaborating and have already managed, together, to select selective DYRK1A inhibitors. What now needs to be done is to establish the proof of their effectiveness on several animal models before carrying out the final selection of the drug candidate and starting a regulatory preclinical assessment before being used for clinical trials…
A promising project seen as a priority by the public authorities…
Under ManRos’s lead, the TRIAD project brings together teams which are respected and renowned for the quality of their work. The fact that these teams are involved in the project is, in itself, a very encouraging scientific validation and testifies of the importance of this research.
Besides, the public authorities are also supporting the implementation of the project in a significant way. TRIAD had, indeed, been selected by the experts of the Ministry of Health within the call
…but most of all for the Foundation
Conscious of the extraordinary opportunity provided by this research programme. The Jérôme Lejeune Foundation, of course, supports ManRos for the TRIAD project. Gathered in assembly last June, the members of the board of directors decided to invest a significant amount into the project to enable Doctor Meijer and Professor Galons to have the necessary means to continue the TRIAD project. This commitment will be determining for its smooth running and the development of quick innovative research solutions.