Treatment with valproic acid ameliorates ADHD symptoms in fragile X syndrome boys
| Autor: | Francesca Romana Di Raimo, Julie A Hutchison, Chiara Setini, Mike Snape, Francesca Bevilacqua, Silvia Vernacotola, Giovanni Neri, Elisabetta Tabolacci, Maria-Giulia Torrioli, Diego Martinelli |
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| Rok vydání: | 2010 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Adolescent medicine.drug_class chemistry.chemical_compound Internal medicine Genetics medicine Attention deficit hyperactivity disorder Humans Child Genetics (clinical) Valproic Acid biology business.industry Mood stabilizer medicine.disease FMR1 Demethylating agent Fragile X syndrome Histone Deacetylase Inhibitors Histone Endocrinology chemistry Attention Deficit Disorder with Hyperactivity Fragile X Syndrome biology.protein Anticonvulsants Female Histone deacetylase business medicine.drug |
| Zdroj: | American journal of medical genetics. Part A. (6) |
| ISSN: | 1552-4833 |
| Popis: | Fragile X syndrome (FXS) is the leading cause of inherited mental retardation, due to expansion and methylation of the CGG sequence at the 5' UTR of the FMR1 gene. Around 90% of affected boys present with attention deficit hyperactivity disorder (ADHD), while this percentage is lower in FXS girls (35-47%). Treatment of these behavioral symptoms is critical for many families. In an attempt at identifying drugs capable of restoring the activity of the FMR1 gene, we investigated the use of valproic acid (VPA), a well-known antiepileptic drug, also used as a mood stabilizer and in migraine therapy. It is described as an inhibitor of histone deacetylase (HDAC) and, possibly, as a DNA demethylating agent. In an in vitro study we observed that treatment of lymphoblastoid cells from FXS patients with VPA caused a modest reactivation of FMR1 transcription and increased levels of histone acetylation, confirming the histone hyperacetylating effect, but not its putative DNA demethylating activity. On the basis of these findings, we decided to evaluate the in vivo efficacy of VPA on ADHD symptoms in FXS patients. We observed an improvement in the adaptive behavior, defined as the performance of daily activities required for personal and social competence, due to a significant reduction in hyperactivity after VPA treatment. This treatment could be considered as an alternative to that with stimulants, whose efficacy in patients with FXS needs to be confirmed by further studies. |
| Databáze: | OpenAIRE |
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