CNS Drugs

, Volume 27, Issue 9, pp 679–702 | Cite as

Prospects for Improving Brain Function in Individuals with Down Syndrome

  • Alberto C. S. Costa
  • Jonah J. Scott-McKean
Leading Article


Down syndrome (DS), which results from an extra copy of chromosome 21 (trisomy 21), is the most common genetically defined cause of intellectual disability. Although no pharmacotherapy aimed at counteracting the cognitive and adaptive deficits associated with this genetic disorder has been approved at present, there have been several new promising studies on pharmacological agents capable of rescuing learning/memory deficits seen in mouse models of DS. Here, we will review the available mouse models for DS and provide a comprehensive, albeit not exhaustive review of the following preclinical research strategies: (1) SOD1 and antioxidant agents; (2) APP and γ-secretase inhibitors; (3) DYRK1A and the polyphenol epigallocatechin gallate (EGCG); (4) GIRK2 and fluoxetine; (5) adrenergic receptor agonists; (6) modulation of GABAA and GABAB receptors; (7) agonism of the hedgehog signaling pathway; (8) nerve growth factor (NGF) and other neurotrophic factors; (9) anticholinesterase (AChE) agents; and (10) antagonism of NMDA receptors. Finally, we will review briefly five different strategies in DS that have led to clinical studies that either have been concluded or are currently underway: (1) antioxidant therapy; (2) AChE therapy; (3) green tea extract therapy; (4) RG1662 therapy; and (5) memantine therapy. These are exciting times in DS research. Within a decade or so, it is well into the realm of possibility that new forms of pharmacotherapies might become valuable tools in the armamentarium of developmental clinicians, as adjutants to more traditional and proven forms of habilitative interventions aimed at improving the quality of life of individuals with DS.


NMDA Receptor Nerve Growth Factor Alzheimer Disease Down Syndrome EGCG 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like to thank the following funding agencies: The Colorado Clinical and Translational Institute (CCTSI), Instituto Alana, and The Forest Research Institute (for the Investigator Initiated Grant NAM-58). The authors would also like to thank Jonathan P. Scott-McKean for the artwork of Fig. 1. Authors state that they have no conflict of interest.


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Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  1. 1.Division of Pediatric Neurology, Department of PediatricsCase Western Reserve School of Medicine and Rainbow Babies and Children’s HospitalClevelandUSA

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