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

Neurobiology of Disease

Jun Yang¹  Eva L. Feldman²  Mehdi Gasmi²  Raymond T. Bartus²  Nicholas M. Boulis³  Qingshan Teng³  Sang Su Oh³  Carey Backus⁴  Erin Carlton⁴  Kathie M. Bishop⁴  Colin K. Franz⁵  Thais Federici⁵ 

[1] Department of Neuroscience and Center for Neurological Restoration, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA;Ceregene, Inc., 9381 Judicial Drive, Suite 130, San Diego, CA 92121, USA;Department of Neurology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-0588, USA;Department of Neuroscience and Center for Neurological Restoration, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA;Department of Neurosurgery, Emory University, 1365B Clifton Rd., NE, Ste. 6200 Atlanta, GA 30322, USA;

关键词: Amyotrophic lateral sclerosis;    Insulin-like growth factor-I;    Motor neuron;    Neuroprotection;    Spinal cord;    Gene therapy;   

DOI  :  

来源: DOAJ

【 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 hSOD1G93A 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, hSOD1G93A rats. We conclude that ISC injection of CERE-130 has the potential to protect motor neurons and preserve neuromuscular function in ALS.

【 授权许可】

Unknown