Peer mediation in play settings for minimally verbal students with autism Spectrum disorder.

Background and aims: Peer-mediated interventions (PMIs) are effective strategies to foster socialization of children with autism spectrum disorder (ASD) in natural settings. However, research examining the efficacy of peer mediation for students with ASD who have the greatest cognitive and language impairments remains limited. Additionally, previous studies essentially targeted communicative abilities of participants. To address this gap, the present study evaluated the effects of a play-based PMI on three socio-communicative skills (play, social engagement and imitation) of minimally verbal students with ASD who also have a comorbidity of intellectual disability (ID). Methods: Seven children with ASD attending ordinary school settings and 14 typically developing (TD) preschoolers participated. Seven single-sex groups were formed, and children played together during two 30 min weekly sessions. TD children were trained according to the principles of the integrated play group model. We used a multiple-baseline design across participants to measure the effects of the intervention on play skills, social engagement and motor imitation of students with ASD. Results: Outcomes revealed an intervention effect for most of the participants, despite some variations across children. After the peer training, four children increased their duration of functional/symbolic play, six children improved their duration of interactive play and five children increased their rates of motor imitation. Concerning maintenance gains, inter-individual differences are also important. Conclusions and implications: These findings suggest that a play-based PMI may be a feasible option for targeting inclusive education and improving socio-communicative skills of some minimally verbal students with ASD who also have an ID. However, variations across children invite further research to clarify how individual factors can moderate the effects of PMIs in children with ASD who are the most impaired.

Point-Substitution of Phenylalanine Residues of 26RFa Neuropeptide: A Structure-Activity Relationship Study.

26RFa is a neuropeptide that activates the rhodopsin-like G protein-coupled receptor QRFPR/GPR103. This peptidergic system is involved in the regulation of a wide array of physiological processes including feeding behavior and glucose homeostasis. Herein, the pharmacological profile of a homogenous library of QRFPR-targeting peptide derivatives was investigated in vitro on human QRFPR-transfected cells with the aim to provide possible insights into the structural determinants of the Phe residues to govern receptor activation. Our work advocates to include in next generations of 26RFa(20-26)-based QRFPR agonists effective substitutions for each Phe unit, i.e., replacement of the Phe22 residue by a constrained 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid moiety, and substitution of both Phe24 and Phe26 by their para-chloro counterpart. Taken as a whole, this study emphasizes that optimized modifications in the C-terminal part of 26RFa are mandatory to design selective and potent peptide agonists for human QRFPR.

Rational design of a low molecular weight, stable, potent, and long-lasting GPR103 aza-ß3-pseudopeptide agonist.

26RFa, a novel RFamide neuropeptide, is the endogenous ligand of the former orphan receptor GPR103. Intracerebroventricular injection of 26RFa and its C-terminal heptapeptide, 26RFa((20-26)), stimulates food intake in rodents. To develop potent, stable ligands of GPR103 with low molecular weight, we have designed a series of aza-ß(3)-containing 26RFa((20-26)) analogues for their propensity to establish intramolecular hydrogen bonds, and we have evaluated their ability to increase [Ca(2+)](i) in GPR103-transfected cells. We have identified a compound, [Cmpi(21),aza-ß(3)-Hht(23)]26RFa((21-26)), which was 8-fold more potent than 26RFa((20-26)) in mobilizing [Ca(2+)](i). This pseudopeptide was more stable in serum than 26RFa((20-26)) and exerted a longer lasting orexigenic effect in mice. This study constitutes an important step toward the development of 26RFa analogues that could prove useful for the treatment of feeding disorders.

Structure-activity relationships of a series of analogues of the RFamide-related peptide 26RFa.

26RFa is a new member of the RFamide peptide family that has been identified as the endogenous ligand of the orphan GPCR GPR103. As the C-terminal heptapeptide (26RFa((20-26))) mimics the action of the native peptide on food intake and gonadotropin secretion in rodents, we have synthesized a series of analogues of 26RFa((20-26)) and measured their potency to induce [Ca(2+)](i) mobilization in Gα(16)-hGPR103-transfected CHO cells. Systematic replacement of each residue by an alanine (Ala scan) and its D-enantiomer (D scan) showed that the last three C-terminal residues were very sensitive to the substitutions while position 23 tolerated rather well both modifications. Most importantly, replacement of Ser(23) by a norvaline led to an analogue, [Nva(23)]26RFa((20-26)), that was 3-fold more potent than the native heptapeptide. These new pharmacological data, by providing the first information regarding the structure-activity relationships of 26RFa analogues, should prove useful for the rational design of potent GPR103 receptor ligands with potential therapeutic application.