In vivo gene electroporation of glial cell line-derived neurotrophic factor (GDNF) into skeletal muscle of SOD1 mutant mice.
Motor neurons degenerate with intracellular vacuolar change and eventually disappear in spinal cords of SOD1 mutant mice, resembling human amyotrophic lateral sclerosis (ALS). The GDNF gene was electroporatically transferred into the leg muscles of SOD1 mutant mice and expressed in muscle cells. This gene therapy with GDNF delayed the deterioration of motor performance, being retrogradely transported into spinal motor neurons. However, the number of the motor neurons and survival of the mutant mice were not improved by GDNF treatment. These results indicate that in vivo gene electroporation of GDNF into muscles could be an appropriate therapeutic approach to ameliorate an early dysfunction of motor neurons in SOD1 mutant mice, but further improvement is needed to use this gene transfer as an effective treatment of ALS.
Yamamoto
M
M
Department of Neurology, Nagoya University Graduate School of Medicine, Japan.
Kobayashi
Y
Y
Li
M
M
Niwa
H
H
Mitsuma
N
N
Ito
Y
Y
Muramatsu
T
T
Sobue
G
G
D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D004195:Disease Models, Animal; D018274:Electroporation; D015316:Genetic Therapy / Q000379:methods; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D051379:Mice; D009043:Motor Activity / Q000502:physiology*; D016472:Motor Neuron Disease / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D009046:Motor Neurons / Q000473:pathology; D018482:Muscle, Skeletal / Q000502:physiology; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000235:genetics* / Q000494:pharmacology; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics*; D014162:Transfection
C495039:GDNF protein, human; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D013482:Superoxide Dismutase