On the Promise of Pharmacotherapies Targeted at Cognitive and Neurodegenerative Components of Down Syndrome

2011/01/01 by Alberto C. S. Costa · 2 citations
Medicine · Biochemistry, Genetics and Molecular Biology · Neuroscience · #Down syndrome and intellectual disability research #Genetics and Neurodevelopmental Disorders #Autism Spectrum Disorder Research

paper · pdf · doi:10.1159/000330861

openalex publication_date 2011/01/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Down syndrome (DS) is the phenotypic consequence of trisomy 21 and is the most common genetically defined cause of intellectual disability. The most complete, widely available, and well-studied animal model of DS is the Ts65Dn mouse. Recent preclinical successes in rescuing learning and memory deficits in Ts65Dn mice are legitimate causes for optimism that pharmacotherapies for cognitive deficits in DS might be within reach. This article provides a snapshot of potential pharmacotherapies for DS, with emphasis on our recent results showing that the N-methyl-D-aspartate receptor antagonist memantine can reverse learning and memory deficits in Ts65Dn mice. Because memantine has already been approved for the therapy of Alzheimer's dementia, we have been able to very rapidly translate these results into human research and are currently conducting a 16-week, randomized, double-blind, placebo-controlled evaluation of the efficacy, tolerability and safety of memantine hydrochloride on enhancing the cognitive abilities of young adults with DS. The design and current status of this clinical trial will be discussed, which will be followed by some speculation on the potential impact of this and future clinical trials in the field of DS.

Citations

• Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease
• Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system - too little activation is bad, too much is even worse
• National estimates and race/ethnic‐specific variation of selected birth defects in the United States, 1999–2001

Cited by

• Prospects for Improving Brain Function in Individuals with Down Syndrome
• Down syndrome [wikipedia]

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