Mechanistic principles of antisense targets for the treatment of spinal muscular atrophy

Natalia N. Singh, Brian M. Lee, Christine J. DiDonato, Ravindra N. Singh*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

43 Scopus citations


Spinal muscular atrophy (SMA) is a major neurodegenerative disorder of children and infants. SMA is primarily caused by low levels of SMN protein owing to deletions or mutations of the SMN1 gene. SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of the production of the functional SMN protein due to predominant skipping of exon 7. Several compounds, including antisense oligonucleotides (ASOs) that elevate SMN protein from SMN2 hold the promise for treatment. An ASO-based drug currently under Phase III clinical trial employs intronic splicing silencer N1 (ISS-N1) as its target. Cumulative studies on ISS-N1 reveal a wealth of information with significance to the overall therapeutic development for SMA. Here, the authors summarize the mechanistic principles behind various antisense targets currently available for SMA therapy.

Original languageEnglish (US)
Pages (from-to)1793-1808
Number of pages16
JournalFuture Medicinal Chemistry
Issue number13
StatePublished - Sep 2015

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Pharmacology


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