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A novel NMDA receptor glycine-site partial agonist, GLYX-13, has therapeutic potential for the treatment of autism

Deficits in social approach behavior, rough-and-tumble play, and speech abnormalities are core features of autism that can be modeled in laboratory rats. Human twin studies show that autism has a strong genetic component, and a recent review has identified 99 genes that are dysregulated in human autism. Bioinformatic analysis of these 99 genes identified the NMDA receptor complex as a significant interaction hub based on protein-protein interactions. The NMDA receptor glycine site partial agonist d-clycoserine has been shown to treat the core symptom of social withdrawal in autistic children. Here, we show that rats selectively bred for low rates of play-induced pro-social ultrasonic vocalizations (USVs) can be used to model certain core symptoms of autism. Low-line animals engage in less social contact time with conspecifics, show lower rates of play induced pro-social USVs, and show an increased proportion of non frequency modulated (i.e. monotonous) ultrasonic vocalizations, compared to non-selectively bred random-line animals. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes and the NMDA receptor family was identified as a significant hub. Treatment of low-line animals with the NMDAR glycine site partial agonist GLYX-13 rescued the deficits in play-induced pro-social 50-kHz and reduced monotonous USVs. Thus, the NMDA receptor has been shown to play a functional role in autism, and GLYX-13 shows promise for the treatment of autism.

from Neuroscience and Biobehavioral Reviews

A novel NMDA receptor glycine-site partial agonist, GLYX-13, has therapeutic potential for the treatment of autism

Deficits in social approach behavior, rough-and-tumble play, and speech abnormalities are core features of autism that can be modeled in laboratory rats. Human twin studies show that autism has a strong genetic component, and a recent review has identified 99 genes that are dysregulated in human autism. Bioinformatic analysis of these 99 genes identified the NMDA receptor complex as a significant interaction hub based on protein-protein interactions. The NMDA receptor glycine site partial agonist d-clycoserine has been shown to treat the core symptom of social withdrawal in autistic children. Here, we show that rats selectively bred for low rates of play-induced pro-social ultrasonic vocalizations (USVs) can be used to model certain core symptoms of autism. Low-line animals engage in less social contact time with conspecifics, show lower rates of play induced pro-social USVs, and show an increased proportion of non frequency modulated (i.e. monotonous) ultrasonic vocalizations, compared to non-selectively bred random-line animals. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes and the NMDA receptor family was identified as a significant hub. Treatment of low-line animals with the NMDAR glycine site partial agonist GLYX-13 rescued the deficits in play-induced pro-social 50-kHz and reduced monotonous USVs. Thus, the NMDA receptor has been shown to play a functional role in autism, and GLYX-13 shows promise for the treatment of autism.

from Neuroscience and Biobehavioral Reviews

Phonology and vocal behavior in toddlers with autism spectrum disorders

The purpose of this study is to examine the phonological and other vocal productions of children, 18–36 months, with autism spectrum disorder (ASD) and to compare these productions to those of age-matched and language-matched controls. Speech samples were obtained from 30 toddlers with ASD, 11 age-matched toddlers and 23 language-matched toddlers during either parent–child or clinician–child play sessions. Samples were coded for a variety of speech-like and nonspeech vocalization productions. Toddlers with ASD produced speech-like vocalizations similar to those of language-matched peers, but produced significantly more atypical nonspeech vocalizations when compared to both control groups. Toddlers with ASD show speech-like sound production that is linked to their language level, in a manner similar to that seen in typical development. The main area of difference in vocal development in this population is in the production of atypical vocalizations. Findings suggest that toddlers with ASDs do not tune into the language model of their environment. Failure to attend to the ambient language environment negatively impacts the ability to acquire spoken language.

from Autism Research