Salbutamol increases survival motor neuron (SMN) transcript levels in leucocytes of spinal muscular atrophy (SMA) patients: Relevance for clinical trial design

Francesco Danilo Tiziano, Rosa Lomastro, Anna Maria Pinto, Sonia Messina, Adele D'Amico, Stefania Fiori, Carla Angelozzi, Marika Pane, Eugenio Mercuri, Enrico Bertini, Giovanni Neri, Christina Brahe

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by mutations of the SMN1 gene. Based on severity, three forms of SMA are recognised (types I-III). All patients usually have 2-4 copies of a highly homologous gene (SMN2) which produces insufficient levels of functional survival motor neuron (SMN) protein. Recently, evidence has been provided that SMN2 expression can be enhanced in vitro by salbutamol, a β2-adrenergic agonist. This compound has also been shown to improve motor function of SMA patients in two different pilot trials. Aim: To evaluate the in vivo molecular efficacy of salbutamol in SMA patients. Methods: Twelve type II-III patients took salbutamol orally for 6 months. SMN2 full length transcript levels were determined in peripheral blood leucocytes by absolute real-time PCR, at baseline and after 3 and 6 months of treatment. Results: A significant and constant increase in SMN2 full length transcript levels was detected; the response was directly proportional to SMN2 gene copy number. Conclusions: The data strongly support salbutamol as a candidate for treating SMA, and suggest that SMN2 copy number may predict the molecular response to treatment and may be a useful randomisation parameter in a double blind placebo controlled clinical trial design.

Original languageEnglish
Pages (from-to)856-858
Number of pages3
JournalJournal of Medical Genetics
Volume47
Issue number12
DOIs
Publication statusPublished - Dec 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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