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 output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)447-458
Number of pages12
JournalGenes and Nutrition
Issue number3
Publication statusPublished - Jul 2012


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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Genetics

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  • Cite this

    De Felice, C., Signorini, C., Durand, T., Ciccoli, L., Leoncini, S., D'Esposito, M., Filosa, S., Oger, C., Guy, A., Bultel-Poncé, V., Galano, J. M., Pecorelli, A., De Felice, L., Valacchi, G., & Hayek, J. (2012). Partial rescue of Rett syndrome by ω-3 polyunsaturated fatty acids (PUFAs) oil. Genes and Nutrition, 7(3), 447-458.