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In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate
Author(s) -
Brichta Lars,
Holker Irmgard,
Haug Karsten,
Klockgether Thomas,
Wirth Brunhilde
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20836
Subject(s) - spinal muscular atrophy , valproic acid , smn1 , in vivo , atrophy , motor neuron , medicine , messenger rna , pharmacology , pathology , disease , gene , biology , epilepsy , biochemistry , genetics , psychiatry
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. Interpretation 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.