org-2766 and Autistic-Disorder

A double-blind, placebo-controlled study examined the effects of 6 weeks of treatment with the adrenocorticotropin4-9 analogue ORG-2766 (40 mg/day) on brain event-related potentials (ERPs) of autistic children. In visual and auditory oddball paradigms (with task and nontask conditions), standard (80%), target (10%), and unexpected novel stimuli (10%) were presented. ORG-2766 (a) increased the occipital P3 component of the ERP to visual targets, (b) decreased the occipital P3 component of the ERP to auditory targets, (c) did not affect visual and auditory parietal target P3 components, and (d) also did not affect the A/Pcz/300 to auditory novel stimuli. In addition, ORG-2766 treatment increased the N1 component of the ERP to task-irrelevant auditory stimuli.

Topics: Adolescent; Adrenocorticotropic Hormone; Anticonvulsants; Arousal; Attention; Autistic Disorder; Brain Mapping; Cerebral Cortex; Child; Double-Blind Method; Electroencephalography; Evoked Potentials; Female; Humans; Male; Occipital Lobe; Peptide Fragments

The aim of the present study was to replicate earlier findings of beneficial effects of ORG 2766, an ACTH-(4-9) analog, in autistic children. Fifty children with autism, 7-15 years old and with a Performance IQ of more than 60, participated in a double-blind placebo controlled parallel trial. Active treatment was 40 mg ORG 2766 for 6 weeks. The outcome was assessed on the basis of the Aberrant Behavior Checklist completed by parents and teachers, and by means of a detailed behavioral observation (30 subjects). ORG 2766 failed to improve social and communicative behavior at a group level. The rate of individual response, defined as a reliable change in social withdrawal at home and at school, to ORG 2766 (10 out of 30) and placebo (4 out of 20) was not significant either. The children who responded to ORG 2766, but not those who responded to placebo, manifested significant improvements outside the changes in the defining variables, including a decrease in hyperactivity at school. The responders to ORG 2766 were characterized mainly by a relatively lower PIQ; further by more initial hyperactivity, stereotypies and abnormal speech, and less initial eye contact. The responders to placebo could not be differentiated from the non-responders to placebo. Future studies should examine whether ORG 2766 differentially affects various subtypes of autism.

Topics: Adolescent; Adrenocorticotropic Hormone; Anticonvulsants; Autistic Disorder; Child; Double-Blind Method; Humans; Peptide Fragments; Prognosis; Psychiatric Status Rating Scales; Time Factors

In a double-blind placebo-controlled crossover trial, 14 autistic children were treated with the neuropeptide ORG 2766, a synthetic analog of adrenocorticotrophic hormone (ACTH) (4-9). ORG 2766 treatment (20 mg per day during 4 weeks) was associated with an increased amount and an improved quality of the social interaction of the autistic children with a familiar experimenter. These changes in interaction were clinically relevant. Following treatment with ORG 2766 gaze and smile behaviors of child and experimenter showed stronger temporal contingencies. Further, after ORG 2766, stereotypies were temporally disconnected from verbal initiatives. The data supported the notion of a stimulating effect of ORG 2766 on social interaction. The implications of these findings for the endogenous opioid theory of autism are discussed.

Topics: Adrenocorticotropic Hormone; Autistic Disorder; Child; Child Behavior; Double-Blind Method; Female; Humans; Male; Peptide Fragments

In a second controlled crossover trial, 20 autistic children received 40 mg/day of the neuropeptide ORG 2766, a synthetic analog of ACTH (4-9), for 8 weeks. Parents' checklist ratings (ABC) as well as clinicians' ratings (CGI) pointed to significant improvements after the course of treatment; improvements were clearest on the ABC social withdrawal subscale. The analysis of individual target symptoms and the parents' treatment preferences substantiated the beneficial effects of ORG 2766. In an ethologically analyzed playroom session, ORG 2766 treatment was associated with an improvement in the children's play behavior and a significant increase in the social interaction between child and experimenter. Gaze coordination between child and experimenter also was improved.

Topics: Adolescent; Adrenocorticotropic Hormone; Anticonvulsants; Autistic Disorder; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Peptide Fragments; Personality Assessment; Social Behavior

Fourteen children (12 infantile autism full syndrome present, 2 atypical pervasive developmental disorder) between 5 and 13 years of age participated in a double-blind placebo-controlled cross-over trial. Each child received 20 mg Org 2766 (synthetic analog of ACTH 4-9)/day during 4 weeks, or placebo in a randomly assigned sequence. Drug effects were monitored by ethological playroom observation and by Aberrant Behavior Checklist ratings by parents and teachers. Data of the playroom observation pointed to an activating influence of Org 2766, as revealed by a significant decrease of stereotypic behavior and significant increases in "change toys," "locomote," and "talk." Checklist ratings did not show significant changes. The clinical implications of these findings are discussed.

Topics: Adrenocorticotropic Hormone; Anticonvulsants; Attention; Autistic Disorder; Child; Child Development Disorders, Pervasive; Double-Blind Method; Female; Humans; Male; Motor Activity; Peptide Fragments; Single-Blind Method; Social Environment; Stereotyped Behavior

When charting the structure of the social behavior of autistic children by means of an ethologically analyzed playroom session, deficits appeared in the reciprocity of eye-contact and in the location of verbal initiatives. These deficits in social behavior were beneficially influenced by treatment with the adrenocorticotrophic hormone (4-9) analog ORG 2766.

Topics: Adrenocorticotropic Hormone; Adult; Anticonvulsants; Autistic Disorder; Humans; Intellectual Disability; Intelligence; Peptide Fragments; Social Behavior; Stereotyped Behavior