This week in therapeutics

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Target/marker/pathway

Summary

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Publication and contact information

Neurology

Ataxia

Ribosomal protein S6 kinase 90 kDa polypeptide 5 (RPS6KA5; MSK1); ataxin 1 (ATXN1)

Fly and mouse studies suggest inhibiting MSK1 could help treat spinocerebellar ataxia type 1 (SCA1), which is caused by a polyglutamine expansion in ATXN1. Fly- and human cell-based screens identified MSK1 as a gene in which knockdown leads to decreased levels of mutant ATXN1 and mutant ATXN1-associated toxicity. In mice, small molecule inhibitors of the Mapk pathway or MSK1 decreased Atxn1 levels compared with vehicle. In a mouse model for SCA1, a deficiency in Rps6ka5 resulted in less neurodegeneration than no deficiency. Next steps include developing brain-permeable MSK1 inhibitors and conducting additional screens for modifiers of other proteins associated with neurodegenerative disease.

SciBX 6(25); doi:10.1038/scibx.2013.632
Published online June 27, 2013

Patent application filed; available for licensing

Park, J. et al. Nature;
published online May 29, 2013;
doi:10.1038/nature12204
Contact: Huda Y. Zoghbi, Baylor College of Medicine, Houston, Texas
e-mail:
hzoghbi@bcm.edu