Galantamine efficacy and tolerability as an augmentative therapy in autistic children: A randomized, double-blind, placebo-controlled trial

Traduction partielle: G.M.

J Psychopharmacol. 2013 Oct 15.

Efficacité et tolérance de la galantamine comme une thérapie de suppléance chez les enfants autistes : Un étude en double aveugle randomisée , contrôlée contre placebo

Ghaleiha A, Ghyasvand M, Mohammadi MR, Farokhnia M, Yadegari N, Tabrizi M, Hajiaghaee R, Yekehtaz H, Akhondzadeh S.

Source

1Research Center for Behavioral Disorders and Substance Abuse, Hamadan University of Medical Sciences, Hamadan, Iran.

Abstract

Le rôle des anomalies cholinergiques dans l'autisme a été récemment démontré et il y a un intérêt croissant dans la modulation cholinergique, émergeant pour cibler les symptômes autistiques. La galantamine est un inhibiteur de l'acétylcholinestérase et un potentialisateur allostérique des récepteurs nicotiniques.

Cette étude visait à évaluer les effets possibles de la galantamine comme une thérapie de suppléance à la rispéridone, chez les enfants autistes.

The role of cholinergic abnormalities in autism was recently evidenced and there is a growing interest in cholinergic modulation, emerging for targeting autistic symptoms. Galantamine is an acetylcholinesterase inhibitor and an allosteric potentiator of nicotinic receptors. 
This study aimed to evaluate the possible effects of galantamine as an augmentative therapy to risperidone, in autistic children.

 In this randomized, double-blind, placebo-controlled, parallel-group study, 40 outpatients aged 4-12 years whom had a diagnosis of autism (DSM IV-TR) and a score of 12 or higher on the Aberrant Behavior Checklist-Community (ABC-C) Irritability subscale were equally randomized to receive either galantamine (up to 24 mg/day) or placebo, in addition to risperidone (up to 2 mg/day), for 10 weeks. We rated participants by ABC-C and a side effects checklist, at baseline and at weeks 5 and 10. By the study endpoint, the galantamine-treated patients showed significantly greater improvement in the Irritability (P = 0.017) and Lethargy/Social Withdrawal (P = 0.005) subscales than the placebo group. 

La différence entre les deux groupes dans la fréquence des effets secondaires n'est pas significative. En conclusion, l'augmentation galantamine s'est révélée être une stratégie améliorée relativement sûre et efficace pour soulager certains des symptômes liés à l'autisme.

PMID: 24132248

Acetylcholine Elevation Relieves Cognitive Rigidity and Social Deficiency in a Mouse Model of Autism

Traduction partielle : G.M.

Neuropsychopharmacology. 2013 Oct 7. doi: 10.1038/npp.2013.274. [Epub ahead of print]

L'augmentation de l'acétylcholine allège la  rigidité cognitive et le déficit social dans un modèle murin de l'autisme

Karvat G, Kimchi T.

Source

Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.

Abstract

Autism spectrum disorders (ASD) is defined by behavioral deficits in social interaction, communication, repetitive stereotyped behaviors and restricted interests/ cognitive rigidity. Recent studies in humans and mice suggested that dysfunction of the cholinergic system may underlie autism-related behavioral symptoms. Here we tested the hypothesis that augmentation of acetylcholine in the synaptic cleft by inhibiting acetylcholinesterase may ameliorate autistic phenotypes. We first administered the acetylcholinesterase inhibitor (AChEI) Donepezil systemically by intraperitoneal (i.p.) injections. Second, the drug was injected directly into the rodent homologue of the caudate nucleus, the dorso-medial-striatum (DMS), of the inbred mouse strain BTBR T+tf/J (BTBR), a commonly-used model presenting all core autism-related phenotypes and expressing low brain acetylcholine levels. We found that i.p. injection of AChEI to BTBR mice significantly relieved autism-relevant phenotypes, including decreasing cognitive rigidity, improving social preference and enhancing social interaction, in a dose dependent manner. Microinjection of the drug directly into the DMS, but not into the ventromedial striatum, led to significant amelioration of the cognitive-rigidity and social-deficiency phenotypes. 
Pris ensemble, ces résultats fournissent la preuve du rôle clé du système cholinergique et du stratium dorso-medial dans l'étiologie des TSA, et suggèrent que la flexibilité cognitive élevée peut provoquer une attention sociale accrue.
L'effet thérapeutique potentiel de AChEIs chez les patients atteints de TSA est discutée.

PMID: 24096295