Molecular, genetic and stem cell-mediated therapeutic strategies for spinal muscular atrophy (SMA)

J Cell Mol Med. 2014 Feb;18(2):187-96. doi: 10.1111/jcmm.12224. Epub 2014 Jan 8.

Abstract

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease. It is the first genetic cause of infant mortality. It is caused by mutations in the survival motor neuron 1 (SMN1) gene, leading to the reduction of SMN protein. The most striking component is the loss of alpha motor neurons in the ventral horn of the spinal cord, resulting in progressive paralysis and eventually premature death. There is no current treatment other than supportive care, although the past decade has seen a striking advancement in understanding of both SMA genetics and molecular mechanisms. A variety of disease modifying interventions are rapidly bridging the translational gap from the laboratory to clinical trials. In this review, we would like to outline the most interesting therapeutic strategies that are currently developing, which are represented by molecular, gene and stem cell-mediated approaches for the treatment of SMA.

Keywords: antisense oligonucleotides; gene therapy; induced pluripotent stem cells; molecular therapy; morpholino; spinal muscular atrophy; stem-cell therapy.

Publication types

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

MeSH terms

  • Animals
  • Cell- and Tissue-Based Therapy / methods*
  • Disease Models, Animal
  • Genetic Therapy / methods*
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / physiology
  • Infant
  • Morpholinos / therapeutic use
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Muscular Atrophy, Spinal / genetics
  • Muscular Atrophy, Spinal / metabolism
  • Muscular Atrophy, Spinal / pathology
  • Muscular Atrophy, Spinal / therapy*
  • Mutation
  • Oligonucleotides, Antisense / therapeutic use
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Stem Cell Transplantation*
  • Survival of Motor Neuron 1 Protein / genetics*
  • Survival of Motor Neuron 1 Protein / metabolism

Substances

  • Morpholinos
  • Oligonucleotides, Antisense
  • SMN1 protein, human
  • Survival of Motor Neuron 1 Protein