title: The quest for targeted therapy in fragile X syndrome.
abstract: Fragile X syndrome (FXS) is the most common, monogenetic cause of intellectual disability and autism-spectrum disorders. Although there is no effective therapy, greater understanding of disturbed neuronal pathways has introduced options for targeted therapy. But whereas many FXS phenotypes were improved in preclinical studies with drugs targeting these pathways in the FXS mouse model, attempts to translate these animal-model success stories into treatment of patients in clinical trials have been extremely disappointing. Complicating factors, particularly in animal studies, include mouse inbred strains, variability in functional studies between laboratories, publication bias and lack of reliable and objective primary outcome measures in both mice and patients. Possibly most important, however, is one factor that has been little explored: the complexity of the molecular imbalance in FXS and the need to simultaneously target several different disturbed pathways and different cellular compartments. New, well-conceived animal studies should generate more productive approaches in the quest for targeted therapy for FXS.
authors: a Erasmus MC, Department of Clinical Genetics , P.O. Box 2040, 3000 CA Rotterdam, The Netherlands +31 107 043 152 ; r.willemsen@erasmusmc.nl.
authors: Shimriet
authors: S
authors: Zeidler
authors: a Erasmus MC, Department of Clinical Genetics , P.O. Box 2040, 3000 CA Rotterdam, The Netherlands +31 107 043 152 ; r.willemsen@erasmusmc.nl.
authors: Renate K
authors: RK
authors: Hukema
authors: a Erasmus MC, Department of Clinical Genetics , P.O. Box 2040, 3000 CA Rotterdam, The Netherlands +31 107 043 152 ; r.willemsen@erasmusmc.nl.
authors: Rob
authors: R
authors: Willemsen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015195:Drug Design; D005600:Fragile X Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D010641:Phenotype
keywords: FMR1; fragile X syndrome; outcome measure; preclinical; targeted therapy