Emergence - Emergence

Drug targets for improving cognitive deficits in Down syndrome. – Therapeutics-21

Submission summary

Therapeutics-21 is dedicated to the development of therapeutic molecules aimed at improving cognitive functions in individuals with Down syndrome. The presence of an extra chromosome 21 leads, among other things, to learning and memory deficits that vary between individuals. Currently, medical and paramedical care is given to patients but there is no drug treatment for cognitive deficits per say. Support, education and social integration have significantly changed the quality of life of people with Down syndrome whose life expectancy (55 years old) has doubled in the past 20 years.
The first objective of Therapeutics-21 is to reinforce the concept of a GABA alpha5 inverse agonist, initially developed by Merck Sharp & Dohme for the treatment of Alzheimer ‘s disease, in Down syndrome by completing preclinical studies. Initial preclinical data on acute short term treatment in a mouse model of Down syndrome have already been generated by us, patented and published. We plan to further investigate short and long term effects after chronic treatment in adult and young mice.
The second objective will be to continue to develop new compounds belonging to an innovative chemical series which are inhibitors of Dyrk1a, a kinase involved in the pathophysiology of Down syndrome, localized on chromosome 21 and overexpressed in the disease. We have previously shown that green tea and its main component, EGCG, which are non-selective inhibitors of Dyrk1a, mitigate cognitive deficits in mouse models of Down syndrome. We recently showed the activity and selectivity of this new family of molecules as inhibitors of Dyrk1a in vitro. Following in vitro structure-activity studies on this patentable prototype, we will select the best lead and test its ability to improve cognition in mouse models of Down syndrome.

Project coordinator

Madame Marie-Claude Potier (Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière - CRICM-Equipe Alzheimer's and Prion diseases) – marie-claude.potier@icm-institute.org

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


FIST France Innovation Scientifique et Transfert
CNRS-ICSN Institut de Chimie des Substances Naturelles - équipe 46
BFA-EAC 4413 Biologie Fonctionnelle Adaptative - Equipe d'Accueil Conventionnée 4413
IGBMC Institut de Génétique et de Biologie Moléculaire et Cellulaire - équipe Médecine translationnelle & neurogénétique
CRICM Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière - CRICM-Equipe Alzheimer's and Prion diseases

Help of the ANR 291,346 euros
Beginning and duration of the scientific project: October 2012 - 24 Months

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