Abstract
Recently standardized diagnostic instruments have been developed in diagnostic and therapeutic procedures for Autism Spectrumv Disorders (ASD). According to the DSM-5 criteria, individuals with ASD must show symptoms from early childhood. These symptoms are communication deficits and restricted, repetitive patterns of behaviour. It was recently described by Bioinformatic analysis that 99 modified genes were associated with human autism. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes and the NMDA receptor gene family was identified among these. Using ultrasonic vocalizations, it was demonstrated that genetic variation has a direct impact on the expression of social interactions. It has been proposed that specific alleles interact with a social reward process in the adolescent mouse modifying their social interaction and their approach toward each other. In this review we report that the monoclonal antibody-derived tetrapeptide GLYX-13 was found to act as an N-methyl-D-aspartate receptor modulator and possesses the ability to readily cross the blood brain barrier. Treatment with the NMDAR glycine site partial agonist GLYX-13 rescued the deficit in the animal model. Thus, the NMDA receptor has been shown to play a functional role in autism, and GLYX-13 shows promise for the treatment of autism in autistic children.
Highlights
Autism Spectrum Disorders (ASD) are diseases driven by abnormalities in reciprocal social interaction (SI) and by the limited and repetitive behaviours (American Psychiatric Association, 1994)
In this review we report that the monoclonal antibody-derived tetrapeptide GLYX-13 was found to act as an N-methyl-D-aspartate receptor modulator and possesses the ability to readily cross the blood brain barrier
GLYX 13 belongs to a new class of N-methyl-D-aspartate glutamate receptors (NMDARs) glycine site modulators with therapeutic potential and could have a clinical value
Summary
Autism Spectrum Disorders (ASD) are diseases driven by abnormalities in reciprocal social interaction (SI) and by the limited and repetitive behaviours (American Psychiatric Association, 1994). BioMed Research International [7], and it is characterized by a high affinity for synaptic NMDARs. In several brain regions (hippocampus, thalamus, and neocortex), NMDA receptor glycine/D-serine site is normally not saturated [8, 9] and, in this light, it was shown that the treatments of coagonists produce a modulation of affective behaviours in animal models [10]. The GLYX-13, a tetrapeptide (TPPTamide) originating from that antibody, was found to act as a NMDA receptor modulator similar to the partial agonist D-cycloserine and potentiates learning when administered intravenously to rats undergoing hippocampus-dependent trace eyeblink conditioning. GLYX-13 administration in rats showed enhancements of hippocampus-dependent trace eyeblink conditioning that were similar to those obtained with the antibody B6B21 and with D-cycloserine, the partial agonist of the glycine site on the NMDA receptor. It is worthy to note that chronic administration of DCS can lead to desensitization and the monoclonal antibody B6B21 does not cross the blood brain barrier; instead GLYX-13 crosses the blood brain barrier making it a good candidate for clinical use as a cognitive enhancer
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