Effects of Sertraline Treatment for Young Children with FXS

Selective serotonin reuptake inhibitors (SSRIs) help treat many of the phenotypic manifestations of fragile X syndrome (FXS) including anxiety, sensory processing challenges, and communication and intellectual deficits. However, the efficacy of SSRIs has not been previously studied in children with FXS under five-years-old. The purpose of this study was to elucidate group differences in behavior and developmental outcome measures for young children with FXS when treated with sertraline compared to placebo

Review of targeted treatments in fragile X syndrome

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, and is the leading single-gene cause of autism spectrum disorders. It is due to a loss of the fragile X mental retardation protein, which leads to molecular, behavioral, and cognitive deficits in these patients. Improvements in our understanding of its pathophysiology have led to the development of numerous targeted treatments in FXS as highlighted by metabotropic glutamate receptor antagonists and gamma-Aminobutyric acid receptor modulators. This review will summarize relevant pre-clinical data and results from clinical trials in human subjects with FXS. It will also highlight upcoming studies and future directions for clinical trials as well

Review of targeted treatments in fragile X syndrome

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, and is the leading single-gene cause of autism spectrum disorders. It is due to a loss of the fragile X mental retardation protein, which leads to molecular, behavioral, and cognitive deficits in these patients. Improvements in our understanding of its pathophysiology have led to the development of numerous targeted treatments in FXS as highlighted by metabotropic glutamate receptor antagonists and gamma-Aminobutyric acid receptor modulators. This review will summarize relevant pre-clinical data and results from clinical trials in human subjects with FXS. It will also highlight upcoming studies and future directions for clinical trials as well

General Anesthetic Use in Fragile X Spectrum Disorders.

The fragile X premutation is characterized by a repeat expansion mutation (between 55 to 200 CGG repeats) in the fragile X mental retardation 1 (FMR1) gene, which leads to RNA toxicity at the cellular level. This may cause patients with the premutation to be particularly susceptible to environmental toxins, which could manifest clinically as new or worsening ataxia and memory loss. Multiple published case reports have also suggested general anesthetics as a potential toxin leading to negative side effects when used in patients with fragile X-associated disorders. However, at this time, there have been no formal research studies regarding cellular changes or long-term clinical manifestations after general anesthetic use in this population. This review aims to highlight previous case reports regarding sequelae related to general anesthetic use in fragile X-associated disorders. New case reports related to this phenomenon are also included

A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome

This paper reports on part of the species of the marine isopod genus Serolis (Crustacea, Flabellifera, Serolidae) collected from benthic stations performed during one of the cruises of the Brazil ian Navy Oc/S "Almirante Saldanha" along southern South America. The species reported are Serolis polccris Richardson, 1911, Serolis elliptica Sheppard, 1933, Serolis uaperta Moreira, 1971, and Serolis foresti Bastida & Torti, 1970. A complete synonymy is given for each of these species, as well as the main distinctive characteristics enabling its ready recognition. Some remarks are provided on features not lengthned treated on previous accounts. The geographi cal distribution of all named taxa is given. Serolis uaperta is for the first time reported from off State of Rio Grande do Sul (Brazil) and Uruguay, extending considerably southernwards its southern limit of distribution. Both Serolis foresti and Serolis elliptica are also for the first time recorded from off Uruguay.Estuda-se no presente trabalho parte do total das espécies de isopodes do gênero Sevolis (Crustácea, Flabellifera) coletadas em algumas estações benticas realizadas pelo N/Oc. "Almirante Saldanha" ao largo da costa ocidental da America do Sul. São as seguintes as espécies estudadas: Sevolis polavis Richardson, 1.911, Sevolis elliptioa Sheppard, 1933, Sevolis uapevta Moreira, 1971 e Sevolis fovesti Bastida & Torti, 1970. Para cada espécie é dada completa sinonímia, assim como as principais características, possibilitando sua rápida e fácil identificação. Igualmente, são feitas observações sobre características varias ligeiramente men cionadas em trabalhos anteriores. Sevolis uapevta é pela primeira vez assi nalada ao largo do Estado do Rio Grande do Sul e Uruguai, o que vem estender consideravelmente o limite sul de ocorrência da espécie. Sevolis fovesti e Sevolis elliptica são também, pela primeira vez, registradas ao largo do Uruguai

A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome.

BackgroundGamma-aminobutyric acid (GABA) system deficits are integral to the pathophysiologic development of fragile X syndrome (FXS). Ganaxolone, a GABAA receptor positive allosteric modulator, is hypothesized to improve symptoms such as anxiety, hyperactivity, and attention deficits in children with FXS.MethodsThis study was a randomized, double-blind, placebo-controlled, crossover trial of ganaxolone in children with FXS, aged 6-17 years.ResultsSixty-one participants were assessed for eligibility, and 59 were randomized to the study. Fifty-five participants completed at least the first arm and were included in the intention-to-treat analysis; 51 participants completed both treatment arms. There were no statistically significant improvements observed on the primary outcome measure (Clinical Global Impression-Improvement), the key secondary outcome measure (Pediatric Anxiety Rating Scale-R), or any other secondary outcome measures in the overall study population. However, post-hoc analyses revealed positive trends in areas of anxiety, attention, and hyperactivity in participants with higher baseline anxiety and low full-scale IQ scores. No serious adverse events (AEs) occurred, although there was a significant increase in the frequency and severity of AEs related to ganaxolone compared to placebo.ConclusionsWhile ganaxolone was found to be safe, there were no significant improvements in the outcome measures in the overall study population. However, ganaxolone in subgroups of children with FXS, including those with higher anxiety or lower cognitive abilities, might have beneficial effects.Trial registrationClinicalTrials.gov, NCT01725152