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Intraspinal cord delivery of IGF-I mediated by adeno-associated virus 2 is neuroprotective in a rat model of familial ALS |
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| Authors: | Colin K Franz Thais Federici Jun Yang Carey Backus Sang Su Oh Qingshan Teng Erin Carlton Kathie M Bishop Mehdi Gasmi Raymond T Bartus Eva L Feldman Nicholas M Boulis |
| Institution: | aDepartment of Neurosurgery, Emory University, 1365B Clifton Rd., NE, Ste. 6200 Atlanta, GA 30322, USA;bDepartment of Neuroscience and Center for Neurological Restoration, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA;cCeregene, Inc., 9381 Judicial Drive, Suite 130, San Diego, CA 92121, USA;dDepartment of Neurology, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI 48109-0588, USA |
| Abstract: | BackgroundAmyotrophic 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. |
| Keywords: | Amyotrophic lateral sclerosis Insulin-like growth factor-I Motor neuron Neuroprotection Spinal cord Gene therapy Adeno-associated virus Neurodegeneration Cell death Motor performance hSOD1G93A rat |
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