From Ganfyd

Jump to: navigation, search



Nusinersen is an antisense oligonucleotide that is 2'-O-methoxyethyl phosphorothioate-modified and licensed in the USA and Europe to treat some of the spinal muscle atrophies. These are the ones where lack of expression of functional SMN1 gene product can not be substituted by functional SMN2 due to the common exon 7 dysfunctional mutations of this gene. It an antisense oligonucleotide designed to bind to the SMN2 pre-mRNA and promote inclusion of exon 7 of SMN2. It appears to work as designed when delivered by intrathecal injection to increase functional survival motor neuron protein in motor neurons by altering spicing of SMN2 pre-mRNA[1][2] and as of 2016 had entered phase 3 trials. The first of these reported in 2017[3] by which time gene therapy with scAAV9.CB.hSMN had also reported to be successful in some forms of spinal muscular atrophy.

Clinical Use



Intrathecal 12mg

Clinical Issues

Needs repeat injection of maintenance dose every 4 months. Main side effects are those of lumbar puncture. No long term data on safety.


Cautions and Interactions

Immune reactions to anti-sense RNA is possible and could be severe

Side effects

Special advice


It is an antisense oligonucleotide that increases exon 7 inclusion in SMN2 mRNA transcripts. The SMN2 gene is a poorly functional duplicate in man of the SMN1 gene, but both can produce active protein. Nusinersen does this by binding to an intronic splice silencing site in intron 7 of the SMN2 pre-messenger ribonucleic acid. This displaces splicing factors leading to retention of exon 7. According the usual poor function of SMN2 transcription is corrected and more functional full length SMN protein is produced.