V1a receptor blockade improves social communication in adults with ASD
Treatment with the arginine vasopressin receptor 1A (V1a) antagonist, RG7713, induces subtle improvements in social communication surrogates including eye tracking and affective speech recognition (ASR), among others, in adults with high-functioning autism spectrum disorder (ASD), a study has shown.
The multicentre cross-over study included 19 high-functioning adult male patients with ASD (full scale IQ >70; ABC-Irritability subscale ≤13; mean age 23.4 years). All patients received a single 20 mg dose of RG7713 or placebo administered intravenously as a 2-hour infusion on two different treatment visits (1 and 2), separated by a 7- to 14-day washout period.
Efficacy outcomes included exploratory biomarkers (eye tracking), and behavioural and clinical measures of social cognition and communication (eg, ASR, reading the mind in the eyes, olfactory identification, scripted interaction). Safety and tolerability were also evaluated.
Results showed that treatment with RG7713 produced an increase in biological motion orienting preference in eye tracking (p=0.047) and a nonsignificant improvement in the composite score (p=0.29). The V1a antagonist also reduced the ability to detect lust (p=0.03) and fear (p=0.07) in ASR. However, the reduction was nonsignificant (p=0.59) when all eight individual emotion subscales were combined into an overall ASR performance score.
In terms of safety, a total of 13 adverse events were reported in 10 patients, all of which were mild (11 of 13) or moderate (2 of 13) in severity.
Researchers noted that the observed effects of RG7713 were quantitatively small, and the lack of statistically significant results may suggest that the study was underpowered to detect them.
“Although the 8-hour efficacy assessment window was supported by the drug exposure data (cerebrospinal fluid concentrations remained at approximately the same level during that time, as measured in a phase I single-ascending dose study), some effects may only emerge with longer continuous treatment, and may not be apparent yet, or only partially so, in a single-dose study,” they added. [J Med Chem 2015;58:2275–228]
Notwithstanding, the preliminary findings of the effects of a single 20 mg dose and the use of exploratory biomarkers support further clinical investigation of V1a receptor antagonism as a therapeutic approach to treat core symptoms in ASD, researchers concluded.