title: Evaluation of muscle strength and motor abilities in children with type II and III spinal muscle atrophy treated with valproic acid.
abstract: BACKGROUND
  Spinal muscular atrophy (SMA) is an autosomal recessive disorder that affects the motoneurons of the spinal anterior horn, resulting in hypotonia and muscle weakness. The disease is caused by deletion or mutation in the telomeric copy of SMN gene (SMN1) and clinical severity is in part determined by the copy number of the centromeric copy of the SMN gene (SMN2). The SMN2 mRNA lacks exon 7, resulting in a production of lower amounts of the full-length SMN protein. Knowledge of the molecular mechanism of diseases has led to the discovery of drugs capable of increasing SMN protein level through activation of SMN2 gene. One of these drugs is the valproic acid (VPA), a histone deacetylase inhibitor.
  
  
  METHODS
  Twenty-two patients with type II and III SMA, aged between 2 and 18 years, were treated with VPA and were evaluated five times during a one-year period using the Manual Muscle Test (Medical Research Council scale-MRC), the Hammersmith Functional Motor Scale (HFMS), and the Barthel Index.
  
  
  RESULTS
  After 12 months of therapy, the patients did not gain muscle strength. The group of children with SMA type II presented a significant gain in HFMS scores during the treatment. This improvement was not observed in the group of type III patients. The analysis of the HFMS scores during the treatment period in the groups of patients younger and older than 6 years of age did not show any significant result. There was an improvement of the daily activities at the end of the VPA treatment period.
  
  
  CONCLUSIONS
  Treatment of SMA patients with VPA may be a potential alternative to alleviate the progression of the disease.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01033331.
authors: Department of Neurology, Medical School of the University of São Paulo, São Paulo, Brazil. illorafisio@terra.com.br
authors: Illora A
authors: IA
authors: Darbar
authors: Paulo G
authors: PG
authors: Plaggert
authors: Maria Bernadete D
authors: MB
authors: Resende
authors: Edmar
authors: E
authors: Zanoteli
authors: Umbertina C
authors: UC
authors: Reed
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D053580:Muscle Strength / Q000187:drug effects*; D014897:Spinal Muscular Atrophies of Childhood / Q000188:drug therapy*; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D004791:Enzyme Inhibitors; D014635:Valproic Acid