Molecular therapeutic strategies for spinal muscular atrophies: current and future clinical trials

Clin Ther. 2014 Jan 1;36(1):128-40. doi: 10.1016/j.clinthera.2013.11.006. Epub 2013 Dec 17.


Background: Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease caused by mutations in the survival motor neuron gene (SMN1) and the leading genetic cause of infant mortality. Currently, there is no effective treatment other than supportive care.

Objective: This article provides a general overview of the main aspects that need to be taken into account to design a more efficient clinical trial and to summarize the most promising molecular trials that are currently in development or are being planned for the treatment of SMA.

Methods: A systematic review of the literature was performed, identifying key clinical trials involving novel molecular therapies in SMA. In addition, abstracts presented at the meetings of the Families of Spinal Muscular Atrophy were searched and the Families of Spinal Muscular Atrophy Web site was carefully analyzed. Finally, a selection of SMA clinical trials registered at has been included in the article.

Results: The past decade has seen a marked advancement in the understanding of both SMA genetics and molecular mechanisms. New molecules targeting SMN have shown promise in preclinical studies, and various clinical trials have started to test the drugs that were discovered through basic research.

Conclusions: Both preclinical and early clinical trial results involving novel molecular therapies suggest that the clinical care paradigm in SMA will soon change.

Keywords: ISIS-SMN(Rx); clinical trials; gene therapy; olesoxime; oligonucleotides; small molecules; spinal muscular atrophy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Clinical Trials as Topic
  • Genetic Therapy*
  • Humans
  • Molecular Targeted Therapy
  • Muscular Atrophy, Spinal / drug therapy
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / therapy*
  • Survival of Motor Neuron 1 Protein / genetics*
  • Survival of Motor Neuron 2 Protein / genetics


  • SMN1 protein, human
  • SMN2 protein, human
  • Survival of Motor Neuron 1 Protein
  • Survival of Motor Neuron 2 Protein