Research ArticleMuscular Dystrophy

CDK12 inhibition reduces abnormalities in cells from patients with myotonic dystrophy and in a mouse model

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Science Translational Medicine  29 Apr 2020:
Vol. 12, Issue 541, eaaz2415
DOI: 10.1126/scitranslmed.aaz2415

Muscling in on myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is a genetic muscular disorder caused by accumulation of nuclear foci due to CTG repeat expansion in the DMPK gene. Current therapies only target individual symptoms. Now, Ketley et al. set out to identify targets for reducing the accumulation of nuclear foci. The authors showed that cyclin-dependent kinase 12 (CDK12) is increased in muscle biopsies from patients with DM1 and its inhibition with a small molecule reduced the accumulation of nuclear foci and mutant transcripts. In a mouse model of DM1, CDK12 inhibition reduced nuclear foci and improved myotonia. The results suggest that CDK12 might be a good therapeutic target for treating DM1.

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