LMI070 is an SMN2 splice modulator.1 It selectively enhances SMN2 splicing by stabilizing the complex formed by the U1 small nuclear ribonucleic protein (snRNP) and SMN2 pre-mRNA. LMI070 (3-30 mg/kg) increases the expression of the full-length SMN2 trancript and, at doses ranging from 0.3 to 30 mg/kg, increases SMN protein levels in the brain and spinal cord in the C/+ mouse model of spinal muscular atrophy (SMA).1,2 It also increases survival of SMNΔ7 mice, a model of severe SMA, when administered at doses of 1 and 3 mg/kg.1
1.Palacino, J., Swalley, S.E., Song, C., et al.SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA miceNat. Chem. Biol.11(7)511-517(2015) 2.Cheung, A.K., Hurley, B., Kerrigan, R., et al.Discovery of small molecule splicing modulators of survival motor neuron-2 (SMN2) for the treatment of spinal muscular atrophy (SMA)J. Med. Chem.61(24)11021-11036(2018)