Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS

被引：93

作者：

Lepore, Angelo C. ^{[1
]}

Haenggeli, Christine ^{[1
]}

Gasmi, Mehdi ^{[3
]}

Bishop, Kathie M. ^{[3
]}

Bartus, Raymond T. ^{[3
]}

Maragakis, Nicholas J. ^{[1
]}

Rothstein, Jeffrey D. ^{[1
,2
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA

[2] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA

[3] Ceregene Inc, San Diego, CA USA

来源：

BRAIN RESEARCH | 2007年 / 1185卷

关键词：

adeno-associated virus; insulin-like growth factor 1; gene therapy; neurodegeneration; amyotrophic lateral sclerosis; neuroprotection;

D O I：

10.1016/j.brainres.2007.09.034

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The potent neuroprotective activities of neurotrophic factors, including insulin-like growth factor 1 (IGF-1), make them promising candidates for treatment of amyotrophic lateral sclerosis (ALS). In an effort to maximize rate of motor neuron transduction, achieve high levels of spinal IGF-1 and thus enhance therapeutic benefit, we injected an adeno-associated virus 2 (AAV2)-based vector encoding human IGF-1 (CERE-130) into lumbar spinal cord parenchyma of SOD1(G93A) mice. we observed robust and long-term intraspinal IGF-1 expression and partial rescue of lumbar spinal cord motor neurons, as well as sex-specific delayed disease onset, weight loss, decline in hindlimb grip strength and increased animal survival. (C) 2007 Elsevier B.V. All rights reserved.

引用

页码：256 / 265

页数：10

共 62 条

[1] Increased survival and function of SOD1 mice after glial cell-derived neurotrophic factor gene therapy [J].

Acsadi, G ;

Anguelov, RA ;

Yang, HB ;

Toth, G ;

Thomas, R ;

Jani, A ;

Wang, YY ;

Ianakova, E ;

Mohammad, S ;

Lewis, RA ;

Shy, ME .

HUMAN GENE THERAPY, 2002, 13 (09) :1047-1059

[2] Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients [J].

Aebischer, P ;

Schluep, M ;

Deglon, N ;

Joseph, JM ;

Hirt, L ;

Heyd, B ;

Goddard, M ;

Hammang, JP ;

Zurn, AD ;

Kato, AC ;

Regli, F ;

Baetge, EE .

NATURE MEDICINE, 1996, 2 (06) :696-699

[3] Gene therapy for amyotrophic lateral sclerosis and other motor neuron diseases [J].

Alisky, JM ;

Davidson, BL .

HUMAN GENE THERAPY, 2000, 11 (17) :2315-2329

[4]

ARAKAWA Y, 1990, J NEUROSCI, V10, P3507

[5] Increased motoneuron survival and improved neuromuscular function in transgenic ALS mice after intraspinal injection of an adeno-associated virus encoding bcl-2 [J].

Azzouz, M ;

Hottinger, A ;

Paterna, JC ;

Zurn, AD ;

Aebischer, P ;

Büeler, H .

HUMAN MOLECULAR GENETICS, 2000, 9 (05) :803-811

[6] VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model [J].

Azzouz, M ;

Ralph, GS ;

Storkebaum, E ;

Walmsley, LE ;

Mitrophanous, KA ;

Kingsman, SM ;

Carmeliet, P ;

Mazarakis, ND .

NATURE, 2004, 429 (6990) :413-417

[7]

Beck CW, 2001, GENOME BIOL, V2

[8] Delayed application of IGF-1 and GDNF can rescue already injured postnatal motor neurons [J].

Bilak, MM ;

Kuncl, RW .

NEUROREPORT, 2001, 12 (11) :2531-2535

[9] Gene therapy for ALS delivers [J].

Boillée, S ;

Cleveland, DW .

TRENDS IN NEUROSCIENCES, 2004, 27 (05) :235-238

[10] Onset and progression in inherited ALS determined by motor neurons and microglia [J].

Boillee, Severine ;

Yamanaka, Koji ;

Lobsiger, Christian S. ;

Copeland, Neal G. ;

Jenkins, Nancy A. ;

Kassiotis, George ;

Kollias, George ;

Cleveland, Don W. .

SCIENCE, 2006, 312 (5778) :1389-1392

← 1 2 3 4 5 6 7 →