1. Carrette LLG, Wang CY, Wei C, Press W, Ma W, Kelleher RJ, 3rd, Lee JT. {{A mixed modality approach towards Xi reactivation for Rett syndrome and other X-linked disorders}}. {Proc Natl Acad Sci U S A};2017 (Dec 27)
The X-chromosome harbors hundreds of disease genes whose associated diseases predominantly affect males. However, a subset, including neurodevelopmental disorders, Rett syndrome (RTT), fragile X syndrome, and CDKL5 syndrome, also affects females. These disorders lack disease-specific treatment. Because female cells carry two X chromosomes, an emerging treatment strategy has been to reawaken the healthy allele on the inactive X (Xi). Here, we focus on methyl-CpG binding protein 2 (MECP2) restoration for RTT and combinatorially target factors in the interactome of Xist, the noncoding RNA responsible for X inactivation. We identify a mixed modality approach combining an Xist antisense oligonucleotide and a small-molecule inhibitor of DNA methylation, which, together, achieve 30,000-fold MECP2 up-regulation from the Xi in cultured cells. Combining a brain-specific genetic Xist ablation with short-term 5-aza-2′-deoxycytidine (Aza) treatment models the synergy in vivo without evident toxicity. The Xi is selectively reactivated. These experiments provide proof of concept for a mixed modality approach for treating X-linked disorders in females.
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2. de Castilho LS, Abreu M, Pires ESLGA, Romualdo LTA, Souza ESME, Resende VLS. {{Factors associated with anterior open bite in children with developmental disabilities}}. {Spec Care Dentist};2017 (Dec 26)
AIM: To investigate factors associated with anterior open bite in individuals aged from 2 to 33 years with developmental disabilities. DESIGN: This is a cross-sectional study. A total of 271 dental records were examined. The anterior open bite analyzed was determined based on clinic exam. These variables were also analyzed: gender, age, education level of mother, International Code of Diseases (ICD), mouth breathing, use of anticonvulsant drugs, hyperkinesis, pacifier use, thumb sucking, seizure, and involuntary movements. For the purposes of analysis, the individuals were categorized as being with and without anterior open bite. Variables with a p-value of < 0.25 in the bivariate analysis were incorporated into the logistic regression models. RESULTS: Mouth breathers had a 2.60-fold (95% CI: 1.35-5.01) greater chance of exhibiting anterior open bite than nasal breathers. Pacifier users are more likely to have an anterior open bite (3.32-fold, 95% CI: 1.62-6.77). Individuals with reported involuntary movements had a 2.66-fold (95% CI: 1.26-5.63) greater chance of exhibiting anterior open bite. Users of anticonvulsants drugs had a 3.05 (95% CI: 1.57-5.92) greater chance of showing anterior open bite. CONCLUSION: Involuntary movements, mouth breathing, using anticonvulsant drugs, and using pacifier are factors associated with anterior open bite in patients with developmental disabilities. Lien vers le texte intégral (Open Access ou abonnement)
3. Gasparotto FM, Liveror FA, Tolouei Menegati SEL, Junior AG. {{Herbal Medicine as an Alternative Treatment in Autism Spectrum Disorder: A Systematic Review}}. {Curr Drug Metab};2017 (Dec 27)
This review focuses on the efficacy and safety of herbal medicines in the management of autism spectrum disorder (ASD) in humans and animals. PubMed, Scopus, Google Scholar, Web of Science, and Science Direct databases were searched up to October 30, 2016. The key terms used were « ASD », « Asperger », « autism », « healing plants », « herbal medicine », and « medicinal plants ». In each database, the searches consisted of each of the three key terms describing the disorder and subtypes plus each of the terms describing the therapy. All human and animal studies on the effects of herbs with the key outcome of change in autism symptoms were included. In vitro studies were excluded. From the publications perused in the initial database, 3157 results were identified, reviewed and a total of 23 studies were included. Preclinical studies using critically validated models were conducted, with some promising preliminary results. Data availability on controlled clinical studies is currently very limited. The use of different methodologies and the very small number of patients raise doubts about the effects of these preparations. Available data do not yet allow us to suggest the effectiveness of herbal medicines as an add-on in the treatment of ASD symptoms.
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4. Godoy-Gimenez M, Gonzalez-Rodriguez A, Canadas F, Estevez AF, Sayans-Jimenez P. {{Psychometric Properties of the Spanish Version of the Broad Autism Phenotype Questionnaire: Strengths, Weaknesses, and Future Improvements}}. {J Autism Dev Disord};2017 (Dec 27)
The Broad autism phenotype (BAP) refers to a set of subclinical behavioural characteristics qualitatively similar to those presented in Autism spectrum disorders (ASDs). The BAP questionnaire (BAPQ) has been widely used to assess the BAP both in relatives of ASD people and within the general population. The current study presents the first Spanish version of the BAPQ (BAPQ-SP) and analyses its psychometric properties, including validity evidences based on the BAPQ scores relationship with other variables. Our results only support the use of the Aloof and Rigid sub-scales to assess this phenotype, whereas Pragmatic Language sub-scale seems to be the main source of misfit. This research represents a first step in the study of the BAP features in the Spanish population.
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5. Thevenet M, Donde C, Machabert R, Ancona L, Jost C, Georgieff N. {{[A mentalization-based perspective on childhood autism treatment]}}. {Encephale};2017 (Dec 22)
Mentalization is a process by which a subject makes sense of both his own mental representations and of those around him. Disturbances in the mentalization process are found in several psychiatric disorders, notably borderline personality disorders for which mentalization-based treatments (MBT) have been developed and evaluated. Children with Autism Spectrum Disorder (ASD) display a theory of mind impairments, which corresponds to disturbances in the mentalization process. Although no MBT protocol for patients with ASD has been described in the literature, such treatment appears promising to improve theory of mind and functional outcome of these children. In this paper, we propose to discuss the theoretical ground of MBT therapeutic effect in children with ASD without intellectual disabilities and to describe a clinical protocol to test this perspective.
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6. Yang Y, Tian J, Yang B. {{Targeting gut microbiome: A novel and potential therapy for autism}}. {Life Sci};2017 (Dec 22)
Autism spectrum disorder (ASD) is a severely neurodevelopmental disorder that impairs a child’s ability to communicate and interact with others. Children with neurodevelopmental disorder, including ASD, are regularly affected by gastrointestinal problems and dysbiosis of gut microbiota. On the other hand, humans live in a co-evolutionary association with plenty of microorganisms that resident on the exposed and internal surfaces of our bodies. The microbiome, refers to the collection of microbes and their genetic material, confers a variety of physiologic benefits to the host in many key aspects of life as well as being responsible for some diseases. A large body of preclinical literature indicates that gut microbiome plays an important role in the bidirectional gut-brain axis that communicates between the gut and central nervous system. Moreover, accumulating evidences suggest that the gut microbiome is involved in the pathogenesis of ASD. The present review introduces the increasing evidence suggesting the reciprocal interaction network among microbiome, gut and brain. It also discusses the possible mechanisms by which gut microbiome influences the etiology of ASD via altering gut-brain axis. Most importantly, it highlights the new findings of targeting gut microbiome, including probiotic treatment and fecal microbiota transplant, as novel and potential therapeutics for ASD diseases.
