Research ArticleDown Syndrome

Hedgehog Agonist Therapy Corrects Structural and Cognitive Deficits in a Down Syndrome Mouse Model

Science Translational Medicine  04 Sep 2013:
Vol. 5, Issue 201, pp. 201ra120
DOI: 10.1126/scitranslmed.3005983

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Sonic Hedgehog to the Rescue

Down syndrome, or trisomy 21, is one of the most common chromosomal abnormalities and a common cause of intellectual disability. Although there is no way to correct the underlying genetic abnormality in this disease, the abnormalities in brain structure resulting from the chromosomal change may not be so immutable, according to a new study by Das et al.

The authors used a mouse model of Down syndrome to demonstrate that a single dose of a drug that stimulates a signaling pathway called Sonic hedgehog, given shortly after birth, had a number of effects on the mice. The medication improved brain development in treated animals, leading to normalization of cerebellar morphology and some improvement of hippocampal synaptic function by adulthood. Treated mice also exhibited stronger performance on a variety of cognitive tasks involving learning and memory, with results that were often indistinguishable from those of control mice.

The findings of this paper do not imply an imminent cure for Down syndrome or a treatment for human patients in the near future. The effects of Sonic hedgehog on brain development in humans are not yet fully understood, and overactivation of this pathway has been linked to some diseases. Nevertheless, this study provides insights into the biology of Down syndrome and its molecular underpinnings, which may eventually lead to improved therapies for human patients.