Salbutamol increases survival motor neuron (SMN) transcript levels in leucocytes of spinal muscular atrophy (SMA) patients: relevance for clinical trial design. Issue 12 (12th September 2010)

• Record Type: Journal Article
• Authors: Tiziano, Francesco Danilo; Lomastro, Rosa; Pinto, Anna Maria; Messina, Sonia; D'Amico, Adele; Fiori, Stefania; Angelozzi, Carla; Pane, Marika; Mercuri, Eugenio; Bertini, Enrico; Neri, Giovanni; Brahe, Christina
• Is Part Of: Journal of medical genetics. Volume 47:Issue 12(2010)
• Page Start: 856
• Page End: 858
• Publication Date: 2010-09-12
• Subjects: Spinal muscular atrophy -- biomarker -- SMN -- salbutamol -- pilot trial -- molecular genetics -- motor neurone disease -- neuromuscular disease; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2010.080366
• Languages: English
• ISSNs: 1468-6244

Abstract

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.