title: Improvement of the Rett syndrome phenotype in a MeCP2 mouse model upon treatment with levodopa and a dopa-decarboxylase inhibitor.
abstract: Rett Syndrome is a neurodevelopmental autism spectrum disorder caused by mutations in the gene coding for methyl CpG-binding protein (MeCP2). The disease is characterized by abnormal motor, respiratory, cognitive impairment, and autistic-like behaviors. No effective treatment of the disorder is available. Mecp2 knockout mice have a range of physiological and neurological abnormalities that resemble the human syndrome and can be used as a model to interrogate new therapies. Herein, we show that the combined administration of Levodopa and a Dopa-decarboxylase inhibitor in RTT mouse models is well tolerated, diminishes RTT-associated symptoms, and increases life span. The amelioration of RTT symptomatology is particularly significant in those features controlled by the dopaminergic pathway in the nigrostratium, such as mobility, tremor, and breathing. Most important, the improvement of the RTT phenotype upon use of the combined treatment is reflected at the cellular level by the development of neuronal dendritic growth. However, much work is required to extend the duration of the benefit of the described preclinical treatment.
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Karolina
authors.initials: K
authors.lastname: Szczesna
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: de la Caridad
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Paolo
authors.initials: P
authors.lastname: Petazzi
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Soler
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Roa
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Mauricio A
authors.initials: MA
authors.lastname: Saez
authors.affiliation: 1] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain [2] Institute of Neuropathology, University of Barcelona, Barcelona, Spain [3] Center for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Fourcade
authors.affiliation: 1] Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain [2] Institute of Neuropathology, University of Barcelona, Barcelona, Spain [3] Center for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain [4] Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Aurora
authors.initials: A
authors.lastname: Pujol
authors.affiliation: 1] Center for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain [2] Neurometabolic Unit, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Artuch-Iriberri
authors.affiliation: 1] Center for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain [2] Neurometabolic Unit, Hospital Sant Joan de Déu, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Molero-Luis
authors.affiliation: Department of Pathology, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: August
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Dori
authors.initials: D
authors.lastname: Huertas
authors.affiliation: 1] Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain [2] Institucio Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain [3] Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000818:Animals; D018726:Anti-Dyskinesia Agents / Q000494:pharmacology*; D065105:Aromatic Amino Acid Decarboxylase Inhibitors / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D049108:Cell Enlargement / Q000187:drug effects; D003712:Dendrites / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D004195:Disease Models, Animal; D004296:Dopa Decarboxylase / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency* / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009068:Movement / Q000187:drug effects; D010641:Phenotype; D012119:Respiration / Q000187:drug effects; D015518:Rett Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018726:Anti-Dyskinesia Agents; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D007980:Levodopa; D004296:Dopa Decarboxylase