Salbutamol increases SMN mRNA and protein levels in spinal muscular atrophy cells

被引：67

作者：

Angelozzi, C. ^{[1
]}

Borgo, F. ^{[1
]}

Tiziano, F. D. ^{[1
]}

Martella, A. ^{[1
]}

Neri, G. ^{[1
]}

Brahe, C. ^{[1
]}

机构：

[1] Univ Cattolica Sacro Cuore, Inst Med Genet, I-00168 Rome, Italy

来源：

JOURNAL OF MEDICAL GENETICS | 2008年 / 45卷 / 01期

关键词：

D O I：

10.1136/jmg.2007.051177

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder caused by homozygous absence of the survival motor neuron gene (SMN1). All patients have at least one, usually two to four copies of the related SMN2 gene which, however, produce insufficient levels of functional SMN protein due to the exclusion of exon 7 in the majority of SMN2 transcripts. Here, we show that salbutamol, a beta 2-adrenoceptor agonist, determines a rapid and significant increase in SMN2-full length mRNA and SMN protein in SMA fibroblasts, predominantly by promoting exon 7 inclusion in SMN2 transcripts. These data, together with previous clinical findings, provide a strong rationale to investigate further the clinical efficacy of salbutamol in SMA patients.

引用

页码：29 / 31

页数：3

共 21 条

[1] Phenylbutyrate increases SMN expression in vitro:: relevance for treatment of spinal muscular atrophy [J].

Andreassi, C ;

Angelozzi, C ;

Tiziano, FD ;

Vitali, T ;

De Vincenzi, E ;

Boninsegna, A ;

Villanova, M ;

Bertini, E ;

Pini, A ;

Neri, G ;

Brahe, C .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2004, 12 (01) :59-65

[2] Aclarubicin treatment restores SMN levels to cells derived from type I spinal muscular atrophy patients [J].

Andreassi, C ;

Jarecki, J ;

Zhou, JH ;

Coovert, DD ;

Monani, UR ;

Chen, XC ;

Whitney, M ;

Pollok, B ;

Zhang, ML ;

Androphy, E ;

Burghes, AHM .

HUMAN MOLECULAR GENETICS, 2001, 10 (24) :2841-2849

[3] Phenylbutyrate increases SMN gene expression in spinal muscular atrophy patients [J].

Brahe, C ;

Vitali, T ;

Tiziano, FD ;

Angelozzi, C ;

Pinto, AM ;

Borgo, F ;

Moscato, U ;

Bertini, E ;

Mercuri, E ;

Neri, G .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2005, 13 (02) :256-259

[4] Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy [J].

Brichta, L ;

Hofmann, Y ;

Hahnen, E ;

Siebzehnrubl, FA ;

Raschke, H ;

Blumcke, I ;

Eyupoglu, IY ;

Wirth, B .

HUMAN MOLECULAR GENETICS, 2003, 12 (19) :2481-2489

[5] In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate [J].

Brichta, Lars ;

Holker, Irmgard ;

Haug, Karsten ;

Klockgether, Thomas ;

Wirth, Brunhilde .

ANNALS OF NEUROLOGY, 2006, 59 (06) :970-975

[6] Regeneration of peripheral nerves after clenbuterol treatment in a rat model [J].

Frerichs, O ;

Fansa, H ;

Ziems, P ;

Schneider, W ;

Keilhoff, G .

MUSCLE & NERVE, 2001, 24 (12) :1687-1691

[7] Hydroxyurea enhances SMN2 gene expression in spinal muscular atrophy cells [J].

Grzeschik, SM ;

Ganta, M ;

Prior, TW ;

Heavlin, WD ;

Wang, CH .

ANNALS OF NEUROLOGY, 2005, 58 (02) :194-202

[8] ALBUTEROL EXTENDED-RELEASE PRODUCTS - EFFECT OF FOOD ON THE PHARMACOKINETICS OF SINGLE ORAL DOSES OF VOLMAX AND PROVENTIL REPETABS IN HEALTHY MALE-VOLUNTEERS [J].

HUSSEY, EK ;

DONN, KH ;

POWELL, JR ;

LAHEY, AP ;

PAKES, GE .

JOURNAL OF CLINICAL PHARMACOLOGY, 1991, 31 (06) :561-564

[9] Diverse small-molecule modulators of SMN expression found by high-throughput compound screening: early leads towards a therapeutic for spinal muscular atrophy [J].

Jarecki, J ;

Chen, XC ;

Bernardino, A ;

Coovert, DD ;

Whitney, M ;

Burghes, A ;

Stack, J ;

Pollok, BA .

HUMAN MOLECULAR GENETICS, 2005, 14 (14) :2003-2018

[10] Pilot trial of albuterol in spinal muscular atrophy [J].

Kinali, M ;

Mercuri, E ;

Main, M ;

De Biasia, F ;

Karatza, A ;

Higgins, R ;

Banks, LM ;

Manzur, AY ;

Muntoni, F .

NEUROLOGY, 2002, 59 (04) :609-610

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