Expanded CUG repeat region of Dystrophia Myotonica Protein Kinase mRNA (CUGexp-DMPK)

The expanded CUG repeat region of the Dystrophia Myotonica Protein Kinase (DMPK) mRNA is the primary pathogenic driver of Myotonic Dystrophy Type 1 (DM1). In affected individuals, the 3' untranslated region (UTR) of the DMPK gene contains an abnormally high number of CTG repeats, which are transcribed into toxic CUG-expanded mRNA. These expanded repeats form stable hairpin structures that sequester RNA-binding proteins, most notably the Muscleblind-like (MBNL) family, leading to widespread alternative splicing defects (spliceopathy) across various tissues. Therapeutic strategies targeting this region aim to either degrade the toxic mRNA using antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs), or to use small molecules that displace sequestered proteins to restore normal cellular function. Current clinical candidates include antibody-oligonucleotide conjugates designed to enhance delivery to muscle and cardiac tissues, addressing the multisystemic nature of the disease.

Other names

Toxic CUG repeatsDMPK CUG expansionCUG-expanded DMPK mRNADM1 repeat expansionDystrophia myotonica protein kinase 3' UTR repeats

Therapeutic agents target this region to induce RNase H-mediated degradation of the toxic mRNA, utilize RNA interference (RNAi) for transcript knockdown, or employ small molecules and steric-blocking oligonucleotides to displace sequestered Muscleblind-like (MBNL) proteins, thereby restoring normal alternative splicing patterns.