Antisense oligonucleotides to treat spinal muscular atrophy
Shift Pharmaceuticals (University of Missouri)
Abstract for Midwest Drug Development Conference, Sept. 30-Oct. 1, 2019. Omaha NE.
"We have previously characterized a genetic region upstream of SMN2 exon 7 called Element 1 (E1) that functions as a repressor of SMN2 exon 7 inclusion. The presence of this genetic element reduces the production of the full-length SMN product by promoting the exclusion of exon 7 and the expression of the truncated isoform (SMN-delta7). Molecules that block or inhibit the repressive activity of E1 could be envisioned as potential therapies for SMA is they relieve the repression and allow for high levels of full-length SMN expression from the SMN2 gene. To this end, we have developed an antisense oligonucleotide that anneals to the E1 region using the well-characterized Morpholino chemistry for the molecules’ backbone."