title: Establishing a standardized therapeutic testing protocol for spinal muscular atrophy.
abstract: Several mice models have been created for spinal muscular atrophy (SMA); however, there is still no standard preclinical testing system for the disease. We previously generated type III-specific SMA model mice, which might be suitable for use as a preclinical therapeutic testing system for SMA. To establish such a system and test its applicability, we first created a testing protocol and then applied it as a means to investigate the use of valproic acid (VPA) as a possible treatment for SMA. These SMA mice revealed tail/ear/foot deformity, muscle atrophy, poorer motor performances, smaller compound muscle action potential and lower spinal motoneuron density at the age of 9 to 12 months in comparison with age-matched wild-type littermate mice. In addition, VPA attenuates motoneuron death, increases spinal SMN protein level and partially normalizes motor function in SMA mice. These results suggest that the testing protocol developed here is well suited for use as a standardized preclinical therapeutic testing system for SMA.
authors.affiliation: Department of Neurology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Li-Kai
authors.initials: LK
authors.lastname: Tsai
authors.forename: Ming-Shung
authors.initials: MS
authors.lastname: Tsai
authors.forename: Tzer-Bin
authors.initials: TB
authors.lastname: Lin
authors.forename: Wuh-Liang
authors.initials: WL
authors.lastname: Hwu
authors.forename: Hung
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011237:Predictive Value of Tests; D016601:RNA-Binding Proteins / Q000096:biosynthesis; D055532:SMN Complex Proteins; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D014635:Valproic Acid; D006655:Histone Deacetylases