title: Subcutaneous administration of TC007 reduces disease severity in an animal model of SMA.
abstract: BACKGROUND
  Spinal Muscular Atrophy (SMA) is the leading genetic cause of infantile death. It is caused by the loss of functional Survival Motor Neuron 1 (SMN1). There is a nearly identical copy gene, SMN2, but it is unable to rescue from disease due to an alternative splicing event that excises a necessary exon (exon 7) from the majority of SMN2-derived transcripts. While SMNDelta7 protein has severely reduced functionality, the exon 7 sequences may not be specifically required for all activities. Therefore, aminoglycoside antibiotics previously shown to suppress stop codon recognition and promote translation read-through have been examined to increase the length of the SMNDelta7 C-terminus.
  
  
  RESULTS
  Here we demonstrate that subcutaneous-administration of a read-through inducing compound (TC007) to an intermediate SMA model (Smn-/-; SMN2+/+; SMNDelta7) had beneficial effects on muscle fiber size and gross motor function.
  
  
  CONCLUSIONS
  Delivery of the read-through inducing compound TC007 reduces the disease-associated phenotype in SMA mice, however, does not significantly extend survival.
authors: Department of Veterinary Pathobiology, Bond Life Sciences Center, University of Missouri, Columbia MO, USA. virginiamattis@gmail.com
authors: Virginia B
authors: VB
authors: Mattis
authors: Marina Y
authors: MY
authors: Fosso
authors: Cheng-Wei
authors: CW
authors: Chang
authors: Christian L
authors: CL
authors: Lorson
mesh_terms: D000617:Aminoglycosides / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D009048:Motor Skills / Q000187:drug effects; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009134:Muscular Atrophy, Spinal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000378:metabolism; D013194:Staining and Labeling; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D055533:Survival of Motor Neuron 1 Protein; C546326:TC007