title: Translational endpoints in fragile X syndrome.
abstract: Fragile X syndrome (FXS) occurs in less than 10% of the intellectually disabled (ID) population. The cause of FXS is a CGG trinucleotide repeat longer than 200 CGG units within the first exon of the FMR1 gene, which leads to hypermethylation and consequently silencing of the FMR1 gene. The lack of FMR1's gene product, the fragile X mental retardation protein (FMRP) in neurons is the cause of the ID in patients with FXS. FMRP plays an important role in local protein synthesis at the synapse including modulation of synaptic plasticity. The advancing knowledge about the cellular function of FMRP has led to the identification of translational endpoints for future therapeutic intervention strategies. This review highlights the challenging routes to the identification of reliable outcome measures in preclinical studies using both cellular models and Fmr1 knockout mice. Finally, clinical studies carried out to correct intellectual and behavioral deficits in patients with FXS, using a variety of existing and new drugs, are discussed.
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Celine E F
authors.initials: CE
authors.lastname: de Esch
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors.forename: Shimriet
authors.initials: S
authors.lastname: Zeidler
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, the Netherlands. Electronic address: r.willemsen@erasmusmc.nl.
authors.forename: Rob
authors.initials: R
authors.lastname: Willemsen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D018345:Mice, Knockout; D008959:Models, Neurological; D058990:Molecular Targeted Therapy; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D018697:Nootropic Agents / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care
chemical_list: D015415:Biomarkers; D051860:Fragile X Messenger Ribonucleoprotein 1; D018697:Nootropic Agents
keywords: FMR1; Fmr1 KO mouse; Fragile X syndrome; Outcome measures; Therapy