Therapy development for spinal muscular atrophy in SMN independent targets
Journal
Neural Plasticity
Journal Volume
2012
Pages
456478
Date Issued
2012
Author(s)
Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder, leading to progressive muscle weakness, atrophy, and sometimes premature death. SMA is caused by mutation or deletion of the survival motor neuron-1 (SMN1) gene. An effective treatment does not presently exist. Since the severity of the SMA phenotype is inversely correlated with expression levels of SMN, the SMN-encoded protein, SMN is the most important therapeutic target for development of an effective treatment for SMA. In recent years, numerous SMN independent targets and therapeutic strategies have been demonstrated to have potential roles in SMA treatment. For example, some neurotrophic, antiapoptotic, and myotrophic factors are able to promote survival of motor neurons or improve muscle strength shown in SMA mouse models or clinical trials. Plastin-3, cpg15, and a Rho-kinase inhibitor regulate axonal dynamics and might reduce the influences of SMN depletion in disarrangement of neuromuscular junction. Stem cell transplantation in SMA model mice resulted in improvement of motor behaviors and extension of survival, likely from trophic support. Although most therapies are still under investigation, these nonclassical treatments might provide an adjunctive method for future SMA therapy. Copyright ? 2012 Li-Kai Tsai.
SDGs
Other Subjects
apoptosis inhibitor; neurotrophic factor; plastin 3; protein; protein cpg15; Rho kinase inhibitor; survival motor neuron protein; unclassified drug; survival motor neuron protein 1; autosomal recessive disorder; correlation analysis; degenerative disease; disease severity; gene deletion; gene mutation; human; locomotion; muscle strength; muscle weakness; nerve fiber; neuromuscular synapse; nonhuman; phenotype; review; spinal muscular atrophy; stem cell transplantation; survival; animal; cell survival; disease model; drug antagonism; drug delivery system; drug effect; gene therapy; genetics; metabolism; motoneuron; pathology; physiology; stem cell transplantation; Animals; Cell Survival; Disease Models, Animal; Drug Delivery Systems; Genetic Therapy; Humans; Motor Neurons; Muscular Atrophy, Spinal; Stem Cell Transplantation; Survival of Motor Neuron 1 Protein
Type
review