title: Quantification of SMN protein in leucocytes from spinal muscular atrophy patients: effects of treatment with valproic acid.
abstract: BACKGROUND
  Spinal muscular atrophy (SMA) is caused by the homozygous deletion of the survival motor neuron (SMN)1 gene. The nearly identical SMN2 gene produces small amounts of full-length mRNA and functional SMN protein, due to a point mutation in a critical splicing site. Increasing SMN protein production by histone deacetylase inhibiting drugs such as valproic acid (VPA) is an experimental treatment strategy for SMA.
  
  
  OBJECTIVE
  To investigate whether an SMN-specific ELISA could detect changes in SMN protein expression in peripheral blood mononuclear cells (PBMCs) after treatment with VPA.
  
  
  METHODS
  The authors developed a sensitive SMN-specific ELISA. Six patients with SMA types 2 and 3 participated in the study. Recombinant SMN calibration curves were used to calculate SMN protein levels in PBMCs before and after 4&emsp14;months of VPA treatment.
  
  
  RESULTS
  The SMN ELISA was able to detect small differences in SMN protein concentrations, and differences in SMN protein levels in Epstein-Barr virus immortalised lymphocyte cell lines from SMA type 1 and 2 patients, carriers and healthy individuals (p<0.05). The mean SMN protein level in PBMCs from SMA patients was 22% (SD 15%) of the value in a healthy control. VPA treatment resulted in significantly increased SMN protein levels in five out of six SMA patients compared with baseline values (p<0.05), but did not restore SMN levels to normal values.
  
  
  CONCLUSIONS
  SMN protein quantification by this SMN ELISA is a useful additional tool for evaluating the effects of experimental treatment in SMA.
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Neurology, University Medical Centre Utrecht, The Netherlands. s.piepers-2@umcutrecht.nl
authors.forename: Sanne
authors.initials: S
authors.lastname: Piepers
authors.forename: Jan-Maarten
authors.initials: JM
authors.lastname: Cobben
authors.forename: Peter
authors.initials: P
authors.lastname: Sodaar
authors.forename: Marc D
authors.initials: MD
authors.lastname: Jansen
authors.forename: Renske I
authors.initials: RI
authors.lastname: Wadman
authors.forename: Ann
authors.initials: A
authors.lastname: Meester-Delver
authors.forename: Bwee Tien
authors.initials: BT
authors.lastname: Poll-The
authors.forename: Henny H
authors.initials: HH
authors.lastname: Lemmink
authors.forename: John H J
authors.initials: JH
authors.lastname: Wokke
authors.forename: W-Ludo
authors.initials: WL
authors.lastname: van der Pol
authors.forename: Leonard H
authors.initials: LH
authors.lastname: van den Berg
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018682:GABA Agents / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D014897:Spinal Muscular Atrophies of Childhood / Q000188:drug therapy* / Q000378:metabolism*; D055533:Survival of Motor Neuron 1 Protein / Q000378:metabolism*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D018682:GABA Agents; D055533:Survival of Motor Neuron 1 Protein; D014635:Valproic Acid