In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate.
OBJECTIVE
Spinal muscular atrophy results from loss of the survival motor neuron 1 (SMN1) gene and malfunction of the remaining SMN2. We investigated whether valproic acid can elevate human SMN expression in vivo.


METHODS
Blood was collected from 10 spinal muscular atrophy carriers and 20 spinal muscular atrophy patients treated with valproic acid.


RESULTS
Seven of 10 carriers demonstrated increased SMN messenger RNA and protein levels. SMN2 messenger RNA levels were elevated in 7 patients and unchanged or decreased in 13 patients.


CONCLUSIONS
We provide first proof of the in vivo activation of a causative gene by valproic acid in an inherited disease and discuss strategies of monitoring drug response in patients.
Brichta
Lars
L
Institute of Human Genetics, University of Cologne, Cologne, Germany.
Holker
Irmgard
I
Haug
Karsten
K
Klockgether
Thomas
T
Wirth
Brunhilde
B
D017362:Cyclic AMP Response Element-Binding Protein / Q000097:blood* / Q000187:drug effects* / Q000235:genetics; D018682:GABA Agents / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects*; D006579:Heterozygote; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000188:drug therapy* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000097:blood* / Q000187:drug effects* / Q000235:genetics; D010865:Pilot Projects; D012333:RNA, Messenger / Q000097:blood; D016601:RNA-Binding Proteins / Q000097:blood* / Q000187:drug effects* / Q000235:genetics; D055532:SMN Complex Proteins; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; D014635:Valproic Acid / Q000627:therapeutic use*
D017362:Cyclic AMP Response Element-Binding Protein; D018682:GABA Agents; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein; D014635:Valproic Acid