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ABSTRACT: Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron protein SMN. The SMN locus on chromosome 5q13 contains two inverted copies of SMN, called SMN1 and SMN2. In the SMA disease state, various mutations in the SMN1 locus render that protein nonfunctional and induce the disease state. A therapy to either increase the amount of SMN2 product made, or to increase the inclusion of exon 7, has been proposed for the treatment of SMA. Previous probes have worked through non-specific mechanisms of activation (HDAC inhibition, RNA decapping), and effect an increase in protein abundance in both SMN2 and SMN1 reporter cell lines. The present probe ML104 (CID-6404603) appears to operate through a unique mechanism of action, showing an increase in SMN2 protein production in fibroblast line derived from an SMA patient, without having an effect on SMN1 protein production in the analogous cell line. The compound may alter splicing of SMN2 protein, but it has not been evaluated for use in vivo, and mode of action studies are ongoing.