[Effect of valproic acid on SMN protein level in peripheral blood mononuclear cells of patients with spinal muscular atrophy and different SMN2 copy numbers].

OBJECTIVE

Spinal muscular atrophy (SMA) is currently untreatable hereditary disorder caused by few types of mutations in the SMN1 gene and respective lack of gene's product - survival motor neuron protein (SMN). Last decade studies have shown that phenotype of the disorder is substantially influenced by copy numbers of homologous SMN2 gene; also, an ability of valproic acid to increase the level of SMN in vitro and in vivo has been shown. We investigated an effect of valproic acid on SMN level in peripheral blood mononuclear cells derived from patients with SMA and their parents and sought for possible predictors for treatment efficacy.

MATERIAL AND METHODS

We examined 10 children with SMA and 6 their parents as heterozygous carriers of the mutation using appropriate molecular-genetic techniques. Valproic acid was prescribed in 20mg/kg/day during 2 weeks.

RESULTS AND CONCLUSION

There were no correlation between baseline SMN level and SMN2 copy number; both of the markers do not predict SMN level after the treatment with valproic acid. However, all of patients responded to valproic acid treatment with different grades of SMN level increase. Strong intrafamilial correlation was found for the SMN/Β2-microglobulin ratio.