The First Trial of an Antisense Oligonucleotide for Myotonic Dystrophy

This small phase 1–2a trial provides evidence for short-term safety but not effective delivery to skeletal muscles.

Myotonic dystrophy type 1, a multisystem disorder characterized by myotonia, muscle weakness, cardiac conduction abnormalities, and gastrointestinal dysmotility, is caused by expansion of a trinucleotide (CTG) repeat in the untranslated region of the gene for DM1 protein kinase (DMPK). The safety of baliforsen, an antisense oligonucleotide that promotes RNAse-mediated degradation of abnormal DMPK transcripts, was studied in this phase 1–2a manufacturer-sponsored trial. Ambulatory adults 20 to 55 years old with ≥100 CTG repeats in DMPK and grip myotonia were randomized to receive a total of 8 injections over 6 weeks of 100 mg, 200 mg, 300 mg, 400 mg, or 600 mg of baliforsen or placebo per injection (6 to 10 patients per group).

The most commo…

Reviewing Author

Leana Doherty, MD

Disclosures

Editorial BoardsNeurohospitalist Society; InterACTN (Annals of Clinical and Translational Neurology)

Leana Doherty, MD

Disclosures

Editorial BoardsNeurohospitalist Society; InterACTN (Annals of Clinical and Translational Neurology)

The First Trial of an Antisense Oligonucleotide for Myotonic Dystrophy

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Reviewing Author