Treatment of myotonic dystrophy

A method of treating myotonic dystrophy disease or disorders caused by abnormal sequestration of the muscleblind-like RNA-binding protein (MBNL) comprising administering to a subject in need of treatment a modified muscleblind-like (MBNL) polypeptide or a nucleic acid molecule encoding said modified MBNL polypeptide,

• said modified MBNL polypeptide binding the MBNL YGCY RNA motif, with Y representing a pyrimidine, and having a splicing activity reduced by at least 60% as compared to wild-type MBNL protein,
• wherein said modified MBNL polypeptide is not a chimeric peptide consisting of MBNL polypeptide and a targeting moiety,
• wherein said modified MBNL polypeptide lacks the C-terminal domains of wild-type MBNL protein that are responsible for MBNL splicing regulatory activity,
• wherein said modified MBNL polypeptide corresponds to exons 1 to 4 of the wild-type MBNL protein, or has a sequence at least 90% identical to the amino acid sequence corresponding to exons 1 to 4 of the wild-type MBNL protein,
• wherein said wild-type MBNL protein is MBNL2 or MBLN3;
• and
• wherein said modified MBNL polypeptide is optionally further fused to a nuclear localization sequence (NLS) or a nuclear export sequence (NES).