A soluble activin type IIB receptor improves function in a mouse model of amyotrophic lateral sclerosis

被引：69

作者：

Morrison, Brett M. ^{[1
]}

Lachey, Jennifer L. ^{[4
]}

Warsing, Leigh C. ^{[1
]}

Ting, Beverlie L. ^{[1
]}

Pullen, Abigail E. ^{[4
]}

Underwood, Kathryn W. ^{[4
]}

Kumar, Ravindra ^{[4
]}

Sako, Dianne ^{[4
]}

Grinberg, Asya ^{[4
]}

Wong, Vicki ^{[4
]}

Colantuoni, Elizabeth ^{[3
]}

Seehra, Jasbir S. ^{[4
]}

Wagner, Kathryn R. ^{[1
,2
]}

机构：

[1] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA

[2] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD USA

[3] Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA

[4] Acceleron Pharma Inc, Cambridge, MA USA

来源：

EXPERIMENTAL NEUROLOGY | 2009年 / 217卷 / 02期

关键词：

Myostatin; Activin receptor; SOD1; ALS; Treatment; Muscle; QUALITY-OF-LIFE; SKELETAL-MUSCLE MASS; NONINVASIVE VENTILATION; MYOSTATIN PROPEPTIDE; SOD1(G93A) MICE; PRIMARY TARGET; MDX MICE; ALS; RILUZOLE; GENE;

D O I：

10.1016/j.expneurol.2009.02.017

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Amyotrophic lateral sclerosis (ALS) is a neurologic disease characterized by progressive weakness that results in death within a few years of onset by respiratory failure. Myostatin is a member of the TGF-beta superfamily that is predominantly expressed in muscle and acts as a negative regulator Of Muscle growth. Attenuating myostatin has previously been shown to produce increased muscle mass and strength in normal and disease animal models. In this study, a mouse model of ALS (SOD1(G93A) transgenic mice) was treated with a soluble activin receptor, type IIB (ActRIIB.mFc) which is a putative endogenous signaling receptor for myostatin in addition to other ligands of the TGF-beta superfamily. ActRIIB.mFc treatment produces a delay in the onset of weakness, an increase in body weight and grip strength, and an enlargement of muscle size whether initiated pre-symptomatically or after symptom onset. Treatment with ActRIIB.mFc did not increase survival or neuromuscular junction innervation in SOD1(G93A) transgenic mice. Pharmacologic treatment with ActRIIB.mFc was superior in all measurements to genetic deletion of myostatin in SOD1(G93A) transgenic mice. The improved function of SOD1(G93A) transgenic mice following treatment with ActRIIB.mFc is encouraging for the development of TGF-beta pathway inhibitors to increase muscle strength in patients with ALS. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：258 / 268

页数：11

共 34 条

[1]

Benjamin Boben, 2007, Expert Rev Neurother, V7, P1243, DOI 10.1586/14737175.7.10.1243

[2] A CONTROLLED TRIAL OF RILUZOLE IN AMYOTROPHIC-LATERAL-SCLEROSIS [J].

BENSIMON, G ;

LACOMBLEZ, L ;

MEININGER, V ;

BOUCHE, P ;

DELWAIDE, C ;

COURATIER, P ;

BLIN, O ;

VIADER, F ;

PEYROSTPAUL, H ;

DAVID, J ;

MALOTEAUX, JM ;

HUGON, J ;

LATERRE, EC ;

RASCOL, A ;

CLANET, M ;

VALLAT, JM ;

DUMAS, A ;

SERRATRICE, G ;

LECHEVALLIER, B ;

PEUCH, AJ ;

NGUYEN, T ;

SHU, C ;

BASTIEN, P ;

PAPILLON, C ;

DURRLEMAN, S ;

LOUVEL, E ;

GUILLET, P ;

LEDOUX, L ;

ORVOENFRIJA, E ;

DIB, M .

NEW ENGLAND JOURNAL OF MEDICINE, 1994, 330 (09) :585-591

[3] Functional improvement of dystrophic muscle by myostatin blockade [J].

Bogdanovich, S ;

Krag, TOB ;

Barton, ER ;

Morris, LD ;

Whittemore, LA ;

Ahima, RS ;

Khurana, TS .

NATURE, 2002, 420 (6914) :418-421

[4] Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis [J].

Bourke, SC ;

Tomlinson, M ;

Williams, TL ;

Bullock, RE ;

Shaw, PJ ;

Gibson, GJ .

LANCET NEUROLOGY, 2006, 5 (02) :140-147

[5] HISTOGRAPHIC ANALYSIS OF HUMAN MUSCLE BIOPSIES WITH REGARD TO FIBER TYPES .4. CHILDRENS BIOPSIES [J].

BROOKE, MH ;

ENGEL, WK .

NEUROLOGY, 1969, 19 (06) :591-+

[6] Riluzole - A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in amyotrophic lateral sclerosis [J].

Bryson, HM ;

Fulton, B ;

Benfield, P .

DRUGS, 1996, 52 (04) :549-563

[7] A randomized controlled trial of resistance exercise in individuals with ALS [J].

Dal Bello-Haas, V. ;

Florence, J. M. ;

Kloos, A. D. ;

Scheirbecker, J. ;

Lopate, G. ;

Hayes, S. M. ;

Pioro, E. P. ;

Mitsumoto, H. .

NEUROLOGY, 2007, 68 (23) :2003-2007

[8] Direct binding of Smad3 and Smad4 to critical TGFβ-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene [J].

Dennler, S ;

Itoh, S ;

Vivien, D ;

ten Dijke, P ;

Huet, S ;

Gauthier, JM .

EMBO JOURNAL, 1998, 17 (11) :3091-3100

[9] Skeletal Muscle Is a Primary Target of SOD1G93A-Mediated Toxicity [J].

Dobrowolny, Gabriella ;

Aucello, Michela ;

Rizzuto, Emanuele ;

Beccafico, Sara ;

Mammucari, Cristina ;

Bonconpagni, Simona ;

Belia, Silvia ;

Wannenes, Francesca ;

Nicoletti, Carmine ;

Del Prete, Zaccaria ;

Rosenthal, Nadia ;

Molinaro, Mario ;

Protasi, Feliciano ;

Fano, Giorgio ;

Sandri, Marco ;

Musaro, Antonio .

CELL METABOLISM, 2008, 8 (05) :425-436

[10] The value of muscle exercise in patients with amyotrophic lateral sclerosis [J].

Drory, VE ;

Goltsman, E ;

Reznik, JG ;

Mosek, A ;

Korczyn, AD .

JOURNAL OF THE NEUROLOGICAL SCIENCES, 2001, 191 (1-2) :133-137

← 1 2 3 4 →