Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF‐κB‐p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1‐knockout and wild‐type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF‐κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1‐KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF‐κB‐p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1‐knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome.

Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, phisical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms. Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment. Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children–Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. A phase II randomized, double-blind pilot clinical trial. Scope: male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. Instrumentation: clinical data, blood analysis, Wechsler Intelligence Scale for Children–Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011)

The gut microbiota plays an essential role in human health, influencing gut–brain communication. Imbalances in this microbial ecosystem, termed dysbiosis, have been associated with increased gut permeability and gastrointestinal symptoms commonly reported in autism spectrum disorder (ASD), without implying a direct causal role in ASD itself. This study aimed to determine whether alterations in gut microbiota exist in individuals with Fragile X Syndrome (FXS), with or without ASD, compared to ASD patients and neurotypical controls, and to identify microbiota biomarkers associated with these disorders. Stool samples from Caucasian individuals aged 3–18 years belonging to four groups (ASD, FXS, FXS + ASD, and controls) were analysed by amplifying the V3–V4 region of the bacterial 16S rRNA gene to characterize microbiota composition. Significant differences were found among patient groups compared to neurotypical controls, with notable similarities between the ASD and FXS + ASD groups. Additionally, specific microbiota biomarkers were identified for each patient group. These findings suggest that distinct microbiota alterations are associated with FXS and ASD, which may contribute to a more accurate characterization of symptoms in these disorders and could serve as potential biomarkers for assessing neurodevelopmental risk.

Avances en investigación de la discapacidad intelectual de origen genético: tratamientos experimentales en el síndrome X frágil