PHYSCI 121 Lecture Notes - Lecture 11: Exon Skipping, Drisapersen, Eteplirsen
Document Summary
Many boys can be treated with the same exon skipping procedure. Exon skipping can occur in other exons, and these procedures can impact 80% of boys. Exon 51 skipping can rescue 13% of dmd. Anti-sense oligonucleotides with two different backbones in human exon 51 skipping clinical trials. Eteplirsen-sarepta therapeutics (avi: phosphorodiamidate morpholino oligomer, neutrally charged, minimizes off target effects, may be less immune stimulating. Drisapersen biomarin (prosensa/gsk: 2 o-methyl-phosphorothioate oligonucleotide [2"ome(ps), negatively charged, aids with solubility & binding to plasma proteins increases half-life, may be immune stimulating, dose limiting toxicity. Proteins were rescued in the muscle to some degree. Two people got a placebo and the drug respectively. Over time, there was a very well-matched natural history control. 4 independent pathologists confirmed statistically significant change in dystrophin-positive fibers. From sarepta investor update (oct 1, 2015): 30 mg/kg: statistically significant increase of dystrophin- positive fibers from baseline at week.
