TY - JOUR
T1 - Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS
AU - Lepore, Angelo C.
AU - Haenggeli, Christine
AU - Gasmi, Mehdi
AU - Bishop, Kathie M.
AU - Bartus, Raymond T.
AU - Maragakis, Nicholas J.
AU - Rothstein, Jeffrey D.
N1 - Funding Information:
We thank Natalie Perez for assistance with grip strength measurements; Jean Brennan and Ariadne Bolton for assistance with histology; all members of the Rothstein and Maragakis labs for helpful discussion; The ALS Association, The Robert Packard Center for ALS Research and the NIH (grants NS33958; NS41680) for funding; Project ALS for providing SOD1 G93A mice.
PY - 2007/12/14
Y1 - 2007/12/14
N2 - 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 SOD1G93A 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.
AB - 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 SOD1G93A 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.
KW - Adeno-associated virus
KW - Amyotrophic lateral sclerosis
KW - Gene therapy
KW - Insulin-like growth factor 1
KW - Neurodegeneration
KW - Neuroprotection
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U2 - 10.1016/j.brainres.2007.09.034
DO - 10.1016/j.brainres.2007.09.034
M3 - Article
C2 - 17963733
AN - SCOPUS:36448942946
SN - 0006-8993
VL - 1185
SP - 256
EP - 265
JO - Brain research
JF - Brain research
IS - 1
ER -