3 years ago

Prenatal neurogenesis induction therapy normalizes brain structure and function in Down syndrome mice [Neuroscience]

Prenatal neurogenesis induction therapy normalizes brain structure and function in Down syndrome mice [Neuroscience]
Akiko Nakano-Kobayashi, Haruhisa Inoue, Tomoe Sumida, Yuto Sumida, Masatoshi Hagiwara, Takamitsu Hosoya, Suguru Yoshida, Yukiko Okuno, Isao Kii, Tomonari Awaya

Down syndrome (DS) caused by trisomy of chromosome 21 is the most common genetic cause of intellectual disability. Although the prenatal diagnosis of DS has become feasible, there are no therapies available for the rescue of DS-related neurocognitive impairment. A growth inducer newly identified in our screen of neural stem cells (NSCs) has potent inhibitory activity against dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) and was found to rescue proliferative deficits in Ts65Dn-derived neurospheres and human NSCs derived from individuals with DS. The oral administration of this compound, named ALGERNON (altered generation of neurons), restored NSC proliferation in murine models of DS and increased the number of newborn neurons. Moreover, administration of ALGERNON to pregnant dams rescued aberrant cortical formation in DS mouse embryos and prevented the development of abnormal behaviors in DS offspring. These data suggest that the neurogenic phenotype of DS can be prevented by ALGERNON prenatal therapy.

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