Intraspinal cord delivery of IGF-I mediated by adeno-associated virus 2 is neuroprotective in a rat model of familial ALS

被引：55

作者：

Franz, Colin K. ^{[1
]}

Federici, Thais ^{[1
,2
,3
]}

Yang, Jun ^{[2
,3
]}

Backus, Carey ^{[5
]}

Oh, Sang Su ^{[5
]}

Teng, Qingshan ^{[2
,3
]}

Carlton, Erin ^{[2
,3
]}

Bishop, Kathie M. ^{[4
]}

Gasmi, Mehdi ^{[4
]}

Bartus, Raymond T. ^{[4
]}

Feldman, Eva L. ^{[5
]}

Boulis, Nicholas M. ^{[1
,2
,3
]}

机构：

[1] Emory Univ, Dept Neurosurg, Atlanta, GA 30322 USA

[2] Cleveland Clin Fdn, Lerner Res Inst, Dept Neurosci, Cleveland, OH 44195 USA

[3] Cleveland Clin Fdn, Lerner Res Inst, Ctr Neurol Restorat, Cleveland, OH 44195 USA

[4] Ceregene Inc, San Diego, CA 92121 USA

[5] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA

来源：

NEUROBIOLOGY OF DISEASE | 2009年 / 33卷 / 03期

关键词：

Amyotrophic lateral sclerosis; Insulin-like growth factor-I; Motor neuron; Neuroprotection; Spinal cord; Gene therapy; Adeno-associated virus; Neurodegeneration; Cell death; Motor performance; hSOD1(G93A) rat; AMYOTROPHIC-LATERAL-SCLEROSIS; GROWTH-FACTOR-I; MOTOR-NEURON DISEASE; GENE-TRANSFER; SPINAL-CORD; MOUSE MODEL; SUSTAINED EXPRESSION; MOTONEURON SURVIVAL; AXONAL-TRANSPORT; WOBBLER MOUSE;

D O I：

10.1016/j.nbd.2008.12.003

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease that is characterized by the progressive loss of motor neurons. Patients with ALS usually die from respiratory failure due to respiratory muscle paralysis. Consequently, therapies aimed at preserving segmental function of the respiratory motor neurons could extend life for these patients. Insulin-like growth factor-I (IGF-I) is known to be a potent survival factor for motor neurons. In this study we induced high levels of IGF-I expression in the cervical spinal cord of hSOD1(G93A) rats with intraspinal cord (ISC) injections of an adeno-associated virus serotype 2 vector (CERE-130). This approach reduced the extent of motor neuron loss in the treated segments of the spinal cord. However, a corresponding preservation of motor function was observed in male, but not female, hSOD1(G93A) rats. We conclude that ISC injection of CERE-130 has the potential to protect motor neurons and preserve neuromuscular function in ALS. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：473 / 481

页数：9

共 59 条

[1] EFFECTS OF ASTROCYTES, INSULIN AND INSULIN-LIKE GROWTH FACTOR-I ON THE SURVIVAL OF MOTONEURONS INVITRO [J].