CDK12 identified as myotonic dystrophy target

INDICATION: Myotonic dystrophy type 1 (DM1)

Inhibiting the transcription elongation regulator CDK12 could treat DM1, which is caused by CTG repeat expansions in the DMPK gene that result in cellular accumulation of mutant RNA. CDK12 protein levels were 48% higher in vastus lateralis muscle biopsies from four DM1 patients than samples from four healthy volunteers. In a human DM1 fibroblast cell line with one wild-type and one mutant DMPK allele, a CDK12 inhibitor tool compound reduced levels of mutant RNA relative to wild-type RNA. In a mouse model of DM1, dinaciclib -- an inhibitor of multiple CDKs including CDK12 -- improved muscle function in the gastrocnemius quadriceps and lumbar paraspinal muscles. ...