Genes & Nutrition

, Volume 7, Issue 3, pp 447–458 | Cite as

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

  • Claudio De Felice
  • Cinzia Signorini
  • Thierry Durand
  • Lucia Ciccoli
  • Silvia Leoncini
  • Maurizio D’Esposito
  • Stefania Filosa
  • Camille Oger
  • Alexandre Guy
  • Valérie Bultel-Poncé
  • Jean-Marie Galano
  • Alessandra Pecorelli
  • Laura De Felice
  • Giuseppe Valacchi
  • Joussef Hayek
Research Paper

Abstract

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.

Keywords

Rett syndrome MeCP2 Oxidative Stress ω-3 polyunsaturated fatty acids Isoprostanes Nonprotein bound iron Antioxidants 

Abbreviations

AA

Arachidonic acid

AdA

Adrenic acid

CDKL5

Cyclin-dependent kinase-like 5

F2-dihomo-IsoPs

F2-dihomo-isoprostanes

FOXG1

Forkhead box G1

GC/NICI-MS/MS

Gas chromatography/negative ion chemical ionization tandem mass spectrometry

IsoPs

Isoprostanes

MeCP2

Methyl-CpG-binding protein 2

NPBI

Nonprotein bound iron

O.S.

Oxidative stress

RTT

Rett syndrome

Supplementary material

Supplementary material movie 1 (MPG 215 mb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • 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
    • 6
  • Giuseppe Valacchi
    • 7
    • 8
  • Joussef Hayek
    • 9
  1. 1.Neonatal Intensive Care UnitUniversity Hospital Azienda Ospedaliera Universitaria Senese (AOUS) of Siena, S. M. Le Scotte General HospitalSienaItaly
  2. 2.Department of Pathophysiology, Experimental Medicine and Public HealthUniversity of SienaSienaItaly
  3. 3.Institut des Biomolécules Max Mousseron (IBMM)UMR 5247 CNRS, UM I, UM IIMontpellierFrance
  4. 4.Institute of Genetics and Biophysics “Adriano Buzzati Traverso” CNRNapoliItaly
  5. 5.IRCCS NeuromedPozzilliItaly
  6. 6.Multimedia Content Design Master CourseUniversity of FlorenceFlorenceItaly
  7. 7.Department of Evolutionary BiologyUniversity of FerraraFerraraItaly
  8. 8.Department of Food and NutritionKyung Hee UniversitySeoulKorea
  9. 9.Child Neuropsychiatry UnitUniversity Hospital, AOUSSienaItaly

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