title: Partial rescue of Rett syndrome by ω-3 polyunsaturated fatty acids (PUFAs) oil.
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, F(2)-dihomo-isoprostanes, F(3)-isoprostanes, F(4)-neuroprostanes, and F(2)-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.
authors.affiliation: 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, geniente@gmail.com.
authors.forename: Claudio
authors.initials: C
authors.lastname: De Felice
authors.forename: Cinzia
authors.initials: C
authors.lastname: Signorini
authors.forename: Thierry
authors.initials: T
authors.lastname: Durand
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciccoli
authors.forename: Silvia
authors.initials: S
authors.lastname: Leoncini
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Esposito
authors.forename: Stefania
authors.initials: S
authors.lastname: Filosa
authors.forename: Camille
authors.initials: C
authors.lastname: Oger
authors.forename: Alexandre
authors.initials: A
authors.lastname: Guy
authors.forename: Valérie
authors.initials: V
authors.lastname: Bultel-Poncé
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Galano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pecorelli
authors.forename: Laura
authors.initials: L
authors.lastname: De Felice
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek