Partial rescue of Rett syndrome by ω-3 polyunsaturated fatty acids (PUFAs) oil

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• 作者：Claudio De Felice (1)
  Cinzia Signorini (2)
  Thierry Durand (3)
  Lucia Ciccoli (2)
  Silvia Leoncini (2)
  Maurizio D’Esposito (4) (5)
  Stefania Filosa (4) (5)
  Camille Oger (3)
  Alexandre Guy (3)
  Valérie Bultel-Poncé (3)
  Jean-Marie Galano (3)
  Alessandra Pecorelli (2)
  Laura De Felice (7)
  Giuseppe Valacchi (8) (9)
  Joussef Hayek (10)
  
• 关键词：Rett syndrome ; MeCP2 ; Oxidative Stress ; ω ; 3 polyunsaturated fatty acids ; Isoprostanes ; Nonprotein bound iron ; Antioxidants
• 刊名：Genes & Nutrition
• 出版年：2012
• 出版时间：July 2012
• 年：2012
• 卷：7
• 期：3
• 页码：447-458
• 全文大小：372KB
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• 作者单位：Claudio De Felice (1)
  Cinzia Signorini (2)
  Thierry Durand (3)
  Lucia Ciccoli (2)
  Silvia Leoncini (2)
  Maurizio D’Esposito (4) (5)
  Stefania Filosa (4) (5)
  Camille Oger (3)
  Alexandre Guy (3)
  Valérie Bultel-Poncé (3)
  Jean-Marie Galano (3)
  Alessandra Pecorelli (2)
  Laura De Felice (7)
  Giuseppe Valacchi (8) (9)
  Joussef Hayek (10)
  
  1. Neonatal Intensive Care Unit, University Hospital Azienda Ospedaliera Universitaria Senese (AOUS) of Siena, S. M. Le Scotte General Hospital, Viale M. Bracci, 16, 53100, Siena, Italy
  2. Department of Pathophysiology, Experimental Medicine and Public Health, University of Siena, Siena, Italy
  3. Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, UM I, UM II, Montpellier, France
  4. Institute of Genetics and Biophysics “Adriano Buzzati Traverso-CNR, Napoli, Italy
  5. IRCCS Neuromed, Pozzilli, Italy
  7. Multimedia Content Design Master Course, University of Florence, Florence, Italy
  8. Department of Evolutionary Biology, University of Ferrara, Ferrara, Italy
  9. Department of Food and Nutrition, Kyung Hee University, Seoul, Korea
  10. Child Neuropsychiatry Unit, University Hospital, AOUS, Siena, Italy
  
• ISSN：1865-3499

文摘

Evidence of enhanced oxidative stress (O.S.) and lipid peroxidation has been reported in patients with Rett syndrome (RTT), a relatively rare neurodevelopmental disorder progressing in 4-stages, and mainly caused by loss-of-function mutations in the methyl-CpG-binding protein 2. No effective therapy for preventing or arresting the neurologic regression in the disease in its various clinical presentations is available. Based on our prior evidence of enhanced O.S. and lipid peroxidation in RTT patients, herein we tested the possible therapeutic effects of ω-3 polyunsaturated fatty acids (ω-3 PUFAs), known antioxidants with multiple effects, on the clinical symptoms and O.S. biomarkers in the earliest stage of RTT. A total of 20 patients in stage I were randomized (n?=?10 subjects per arm) to either oral supplementation with ω-3 PUFAs-containing fish oil (DHA: 72.9?±?8.1?mg/kg b.w./day; EPA: 117.1?±?13.1?mg/kg b.w./day; total ω-3 PUFAs: 246.0?±?27.5?mg/kg b.w./day) for 6?months or no treatment. Primary outcomes were potential changes in clinical symptoms, with secondary outcomes including variations for five O.S. markers in plasma and/or erythrocytes (nonprotein bound iron, F2-dihomo-isoprostanes, F3-isoprostanes, F4-neuroprostanes, and F2-isoprostanes). A significant reduction in the clinical severity (in particular, motor-related signs, nonverbal communication deficits, and breathing abnormalities) together with a significant decrease in all the examined O.S. markers was observed in the ω-3 PUFAs supplemented patients, whereas no significant changes were evidenced in the untreated group. For the first time, these findings strongly suggest that a dietary intervention in this genetic disease at an early stage of its natural history can lead to a partial clinical and biochemical rescue.