Drug Discovery for Targeted Pharmacotherapy of Fragile X Syndrome
| Autor: | Will Spooren, Sebastian S. Scharf, Fabrizio Gasparini, Lothar Lindemann |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Clinical study design Disease Pharmacology Biology Bioinformatics medicine.disease FMR1 Clinical trial Fragile X syndrome 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Pharmacotherapy chemistry medicine Mavoglurant Trinucleotide repeat expansion 030217 neurology & neurosurgery |
| DOI: | 10.1016/b978-0-12-804461-2.00018-4 |
| Popis: | Fragile X syndrome (FXS) is the most common monogenic form of inherited mental retardation caused by a CGG trinucleotide repeat expansion and transcriptional shutdown of the FMR1 gene. FXS patients present with a complex and often severe neuropsychiatric phenotype with considerable heterogeneity caused in part by varying trinucleotide repeat sizes, as well as somatic and X-chromosomal mosaicism. Early availability of Fmr1 knockout mice and other disease models have been invaluable for understanding the molecular pathophysiology of FXS and for testing potential pharmacological interventions. Recent clinical trials with a GABAB agonist and with mGlu5 inhibitors showed no significant therapeutic benefits in FXS patients in spite of compelling preclinical data suggesting profound and comprehensive therapeutic effects for both modalities. These discrepancies indicate that improving the translation from preclinical results to clinical trial outcomes requires a careful examination of the preclinical disease models, preclinical and clinical outcome measures, as well as clinical trial design. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|