Is there hope for spinal muscular atrophy synthetic pharmacotherapy?

Figures & data

Figure 1. Overview of the administration and the mode of action of nusinersen. (a) The drug is administered into the fluid surrounding the spinal cord in the lumbar region usually between the disc space of L3–L4. The compound can then reach the target cells, the motor neurons. (b) In the nuclei of the motor neurons the synthetic antisense oligonucleotide nusinersen binds specifically to the intronic splicing silencer in intron 7 (ISS-N1) of SMN2 pre-mRNA and prevents the splicing repressor hnRNP A1/A2 from binding (without steric hindrance, binding of hnRNPA1/A2 would cause exon 7 exclusion). Nusinersen leads therefore to the inclusion of SMN2 exon 7, producing the stable, fully functional, full-length SMN (FL-SMN) protein. (only relevant exons are shown, not to scale).