Jean-Christophe ROUX (MMG) achieved his academic education at Claude Bernard University in Lyon France, where he obtained a PhD in Physiology. As a postdoc at the Karolinska Institute, he participated in research on the development of respiratory control at birth and how environmental perturbations could affect it. As part of the human neurogenetics team led by Dr Laurent Villard, Jean-Christophe Roux has been in charge of Rett Syndrome and associated pathologies since 2006. His group is studying mouse models of Mecp2 dysfunctions and his work led to the implementation of two clinical trials (phase 2a) with Rett patients. The first trial deals with the stimulation of the monoaminergic neurotransmission and the second with the trophic support. Recently, he has developed innovative approaches using gene therapy targeting the brain.
Jean-Christophe Introduces Himself
Links to Jean-Christophe Roux https://publons.com/researcher/2178233/jean-christophe-roux/ and on Orcid
https://orcid.org/0000-0002-9721-8844
Relevant publications
Huntingtin phosphorylation governs BDNF homeostasis and improves the phenotype of Mecp2 knockout mice
Yann Ehinger, Julie Bruyère, Nicolas Panayotis, Yah-Se Abada, Emilie Borloz, Valérie Matagne, Chiara Scaramuzzino, Hélène Vitet, Benoit Delatour, Lydia Saidi, Laurent Villard, Frédéric Saudou, Jean-Christophe Roux
Lay summary
Rett syndrome is a severe and intractable neurological disorder caused by mutations of the MECP2 (Methyl CpG binding protein 2) gene, located on the X chromosome. The MECP2 protein fine-tunes the expression of many genes, including brain-derived neurotrophic factor BDNF. BDNF plays a key role in the brain to help neurons survive and connect together. Normalization of BDNF expression only partially rescues the Mecp2 KO (knock out) mouse phenotype. Huntingtin, the protein mutated in Huntington’s disease, serves as a carrier for BDNF vesicles. We used a combination of state-of-the-art technological approaches and found that genetic activation of Huntingtin increases BDNF axonal transport in neurons deficient for Mecp2 protein. We demonstrated that a very slight modification of Huntingtin (phosphorylation) improves the quality of life of a mouse model of Rett syndrome. This study identifies Huntingtin and its phosphorylation as a new therapeutic target in Rett syndrome and demonstrates that activating endogenous BDNF in the appropriate neuronal circuits is more effective than non-specific BDNF overexpression. This treatment increases BDNF availability and synaptic connectivity in vivo, and improves the phenotype and the survival of a mouse model of Rett syndrome even though the treatment was initiated after the mice had already developed symptoms. Stimulation of endogenous cellular pathways may thus be a promising approach for the treatment of people with Rett syndrome.