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 journalArticle

53 Citations (Scopus)

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

Fingerprint

Spinal Muscular Atrophy
Albuterol
Motor Neurons
Leukocytes
Clinical Trials
Spinal Muscular Atrophies of Childhood
Adrenergic Agonists
Gene Dosage
Controlled Clinical Trials
Random Allocation
Genes
Real-Time Polymerase Chain Reaction
Placebos
Mutation
Therapeutics
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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

In: Journal of Medical Genetics, Vol. 47, No. 12, 12.2010, p. 856-858.

Research output: Contribution to journalArticle

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. / Salbutamol increases survival motor neuron (SMN) transcript levels in leucocytes of spinal muscular atrophy (SMA) patients : Relevance for clinical trial design. In: Journal of Medical Genetics. 2010 ; Vol. 47, No. 12. pp. 856-858.
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AU - D'Amico, Adele

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AU - Angelozzi, Carla

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AU - Neri, Giovanni

AU - Brahe, Christina

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