1. Chez M, Low R, Parise C, Donnel T. {{Safety and observations in a pilot study of lenalidomide for treatment in autism}}. {Autism research and treatment}. 2012;2012:291601.
Autism affects 1 : 88 children in the United States. Familial history of autoimmune disease, autoantibodies in the serum of mothers when there is more than one autistic offspring, and neuroglial response in CSF and brain tissue in autistic patients suggest an immunological variable may be associated with this condition. Lenalidomide has the potential to invoke changes in TNF-alpha with less toxicity than thalidomide. This pilot study evaluated lenalidomide at reduction of TNF-alpha and improvement of behavior and language in children with autism with elevated TNF-alpha. Subjects with elevated TNF-alpha were given 2.5 mgs lenalidomide daily for 12-weeks. Pharmacodynamics and safety was evaluated. Changes in language and autistic behaviors after six and twelve weeks were measured. Although statistical significance was not achieved for most measures, there were trends toward improvement. After 6-weeks, mean receptive language increased: 60.67 +/- 12.06 to 65.00 +/- 15.10 (P = 0.11) and symptoms of autism decreased (40.75 +/- 5.96 versus 38.67 +/- 7.90, P = 0.068). After 12-weeks, CSF-TNF-alpha declined 57% +/- 25% from 80.5 +/- 41.03 to 38.0 +/- 31.27 (P = 0.068). Serum TNF-alpha declined 57% (92.50 +/- 68.92 to 40.25 +/- 44.53 (P = 0.048). This study suggests that lenalidomide is tolerated as a treatment by children with autism and should be further studied as a potential agent for cytockine inflammation.
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2. Fujita E, Tanabe Y, Imhof BA, Momoi MY, Momoi T. {{A complex of synaptic adhesion molecule CADM1, a molecule related to Autism Spectrum Disorder, with MUPP1 in the cerebellum}}. {Journal of neurochemistry}. 2012 Sep 20.
Mutations in the synaptic adhesion protein CADM1 (RA175/SynCAM1) are associated with Autism spectrum disorder (ASD), a neurodevelopmental disorder of uncertain molecular origin. Cadm1 knock out (KO) mice exhibit smaller cerebella with decreased number of synapse of Purkinje cells and some ASD-like symptoms, including impaired ultrasonic vocalization. In the present study, we examined the alteration of the Cadm1 synaptic complex in the mouse cerebellum at postnatal stages. The C-terminal peptide of Cadm1 associated with Mupp1 at PDZ(1-5), a scaffold protein containing 13 PDZ domains, which interacted with GABBR2 at PDZ13, but not with PSD-95. The GABBR2 was detected in a set of proteins interacting with Cadm1 C-terminal. Cadm1 co-localized with Mupp1 and GABBR2 on the dendrites of Purkinje cells in the molecular layers of the developing cerebellum and on the dendrites of hippocampal neurons cultured in vitro. These observations suggest that the Cadm1 synaptic receptor complex, including Mupp1-GABBR2, is located on the dendrites of Purkinje cells. The amount of GABBR2 protein but not mRNA was increased in the cerebella of Cadm1 KO mice, suggesting that lack of Cadm1 does not affect transcription of GABBR2 but may stabilize the Mupp1-GABBR2 complex; the Mupp1-GABBR2 interaction may be stabilized by conformational change in Mupp1 or association with other adhesion molecules and by anchorage to the postsynaptic membrane. Up-regulation of GABBR2 in the cerebellum in the absence of CADM1 may be associated with ASD pathogenesis. (c) 2012 The Authors Journal of Neurochemistry (c) 2012 International Society forNeurochemistry.
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3. Gondalia SV, Palombo EA, Knowles SR, Cox SB, Meyer D, Austin DW. {{Molecular Characterisation of Gastrointestinal Microbiota of Children With Autism (With and Without Gastrointestinal Dysfunction) and Their Neurotypical Siblings}}. {Autism Res}. 2012 Sep 20.
Many children with autism spectrum disorders (ASDs) suffer from gastrointestinal problems such as diarrhoea, constipation and abdominal pain. This has stimulated investigations into possible abnormalities of intestinal microbiota in autistic patients. Therefore, we designed this study to identify differences (and/or similarities) in the microbiota of children with autism (without gastrointestinal dysfunction: n = 23; with gastrointestinal dysfunction: n = 28) and their neurotypical siblings (n = 53) who share a similar environment using bacterial tag-encoded FLX amplicon pyrosequencing. Regardless of the diagnosis and sociodemographic characteristics, overall, Firmicutes (70%), Bacteroidetes (20%) and Proteobacteria (4%) were the most dominant phyla in samples. Results did not indicate clinically meaningful differences between groups. The data do not support the hypothesis that the gastrointestinal microbiota of children with ASD plays a role in the symptomatology of ASD. Other explanations for the gastrointestinal dysfunction in this population should be considered including elevated anxiety and self-restricted diets. Autism Res 2012, **: **-**. (c) 2012 International Society for Autism Research, Wiley Periodicals, Inc.
