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Two children with SMA type 1 received, for the first time, these two innovative treatments, which work with different mechanisms of action. Initially treated by nusinersen, they were also treated with onasemnogene abeparvovec-xioi in a second step, because of a high risk of dependence on permanent invasive ventilation. Nusinersen is a 2ʹ-O -methoxyethyl phosphorothioate-modified ASO designed to alter SMN2 pre-mRNA splicing process by inhibiting splicing factor. 186,187 This results in the inclusion of exon 7 into the mRNA thus enhances the production of full-length SMN protein. 186,187 The drug is administered intrathecally by lumbar puncture.. Jun 18, 2021 · The principal pharmacological action mechanism of the 2ʹ-O-methoxyethyl phosphorothioate modified drug nusinersen alters the SMN2 pre-mRNA splicing process by inhibiting splicing factors. 3 Nusinersen increases exon 7 inclusions in survival motor neuron 2 (SMN2) mRNA transcripts, which increases the production of full-length SMN proteins..
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