Type I PRMT inhibitor MS023 promotes SMN2 exon 7 inclusion and synergizes with nusinersen to rescue the phenotype of SMA mice

In our study we have identified MS023, an inhibitor of PRMTs, to increase SMN protein and FL SMN2 transcript levels, and to improve survival and weights of treated SMA mice, alone and in combination with currently approved antisense oligonucleotide. In order to understand the molecular underpinnings of the added benefit provided by the combinatorial treatment, we performed bulk transcriptomic analysis in spinal cords of SMA mice treated with MS023 only, nusinersen only, and MS023 in combination with nusinersen, compared to wild type and SMA littermates. spinal cords of mice, five groups, four biological replicates per group: untreated SMA mice, SMA mice treated with nusinersen, SMA mice treated with MS023, SMA mice treated with nusinersen and MS023, untreated controls