Researchers at the University of Versailles-Saint-Quentin tested antisense oligonucleotides (ASOs) targeting exon 51 skipping of the DMD gene in mdx52 mice, models of Duchenne muscular dystrophy (DMD) with exon 52 deletion, thereby disrupting dystrophin (Dp427) expression in the brain:
- previous work by the same researchers had shown that these ASOs were truly effective in targeting the central nervous system when injected alone via the local-regional route,
- the addition of an AAV-U7 system, designed to increase their local production, did not achieve the expected result, despite using the same intracerebral administration routes and targeting exon 51 of the DMD gene,
- regardless of the capsid chosen for the AAV.
Even though this approach with AAV-U7 allows for real, but modest, re-expression of dystrophin in the brain, the clinical effect is inconclusive in this animal.
