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Antagonism of NMDA receptors as a potential treatment for Down syndrome: a pilot randomized controlled trial.

ABSTRACT: Down syndrome (DS) is the most common genetic cause of intellectual disability. The N-methyl-D-aspartate (NMDA) receptor uncompetitive antagonist, memantine hydrochloride (memantine), has been shown to improve learning/memory and rescue one form of hippocampus synaptic plasticity dysfunction in the best-studied mouse model of DS available, the Ts65Dn mouse. Given the status of memantine as a treatment for Alzheimer's disease (AD) approved by the Food and Drug Administration, the preclinical evidence of potential efficacy in Ts65Dn mice, and the favorable safety profile of memantine, we designed a study to investigate whether the findings in the mouse model could be translated to individuals with DS. In this pilot, proof-of-principle study we hypothesized that memantine therapy would improve test scores of young adults with DS on measures of episodic and spatial memory, which are generally considered to be hippocampus dependent. Accordingly, in this randomized, double-blind, placebo-controlled trial, we compared the effect of 16-week treatment with either memantine or placebo on cognitive and adaptive functions of 40 young adults with DS using a carefully selected set of neuropsychological outcome measures. Safety and tolerability were also monitored. Although no significant differences were observed between the memantine and placebo groups on the two primary outcome measures, we found a significant improvement in the memantine group in one of the secondary measures associated with the primary hypothesis. Only infrequent and mild adverse events were noted.

SUBMITTER: Boada R

PROVIDER: S-EPMC3410988 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Antagonism of NMDA receptors as a potential treatment for Down syndrome: a pilot randomized controlled trial.

Boada R R Hutaff-Lee C C Schrader A A Weitzenkamp D D Benke T A TA Goldson E J EJ Costa A C S AC

Translational psychiatry 20120717

Down syndrome (DS) is the most common genetic cause of intellectual disability. The N-methyl-D-aspartate (NMDA) receptor uncompetitive antagonist, memantine hydrochloride (memantine), has been shown to improve learning/memory and rescue one form of hippocampus synaptic plasticity dysfunction in the best-studied mouse model of DS available, the Ts65Dn mouse. Given the status of memantine as a treatment for Alzheimer's disease (AD) approved by the Food and Drug Administration, the preclinical evid ...[more]

PMID: 22806212

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Antagonism of NMDA receptors as a potential treatment for Down syndrome: a pilot randomized controlled trial.

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Antagonism of NMDA receptors as a potential treatment for Down syndrome: a pilot randomized controlled trial.

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