The challenges of clinical trials in fragile X syndrome
| Autor: | Fabrizio Gasparini, Elizabeth Berry-Kravis, George Apostol, Sébastien Jacquemont, Florian Von Raison, Randi J Hagerman, Baltazar Gomez-Mancilla, Vincent des Portes, Mike Ufer |
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| Přispěvatelé: | Service de génétique médicale, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neuropédiatrie, Université de Lyon-CHU de Lyon |
| Rok vydání: | 2013 |
| Předmět: |
Autism
Review Bioinformatics Medical and Health Sciences GABA [SCCO]Cognitive science chemistry.chemical_compound 0302 clinical medicine Disease modification 2.1 Biological and endogenous factors Autism spectrum disorder Aetiology mGluR5 FMR1 Pediatric Psychiatry Clinical Trials as Topic 0303 health sciences Outcome measures 3. Good health Fragile X syndrome Phenotype Mental Health FMRP Psychology Clinical psychology congenital hereditary and neonatal diseases and abnormalities Child Development Disorders Intellectual and Developmental Disabilities (IDD) AFQ056 03 medical and health sciences Rare Diseases Clinical Research Behavioral and Social Science medicine Animals Humans Mavoglurant Pervasive 030304 developmental biology Pharmacology Arbaclofen Mechanism (biology) Psychology and Cognitive Sciences Neurosciences medicine.disease Brain Disorders Clinical trial Orphan Drug chemistry Child Development Disorders Pervasive Fragile X Syndrome 030217 neurology & neurosurgery |
| Zdroj: | Psychopharmacology Psychopharmacology, 2014, 231, pp.Issue : 6 Pages : 1237-1250. ⟨10.1007/s00213-013-3289-0⟩ Psychopharmacology, vol 231, iss 6 |
| ISSN: | 1432-2072 0033-3158 |
| DOI: | 10.1007/s00213-013-3289-0 |
| Popis: | Rationale Advances in understanding the underlying mechanisms of conditions such as fragile X syndrome (FXS) and autism spectrum disorders have revealed heterogeneous populations. Recent trials of novel FXS therapies have highlighted several challenges including subpopulations with possibly differential therapeutic responses, the lack of specific outcome measures capturing the full range of improvements of patients with FXS, and a lack of biomarkers that can track whether a specific mechanism is responsive to a new drug and whether the response correlates with clinical improvement. Objectives We review the phenotypic heterogeneity of FXS and the implications for clinical research in FXS and other neurodevelopmental disorders. Results Residual levels of fragile X mental retardation protein (FMRP) expression explain in part the heterogeneity in the FXS phenotype; studies indicate a correlation with both cognitive and behavioral deficits. However, this does not fully explain the extent of phenotypic variance observed or the variability of drug response. Post hoc analyses of studies involving the selective mGluR5 antagonist mavoglurant and the GABAB agonist arbaclofen have uncovered significant therapeutic responses following patient stratification according to FMR1 promoter methylation patterns or baseline severity of social withdrawal, respectively. Future studies designed to quantify disease modification will need to develop new strategies to track changes effectively over time and in multiple symptom domains. Conclusion Appropriate selection of patients and outcome measures is central to optimizing future clinical investigations of these complex disorders. |
| Databáze: | OpenAIRE |
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