In vivo gene electroporation of glial cell line-derived neurotrophic factor (GDNF) into skeletal muscle of SOD1 mutant mice

• Published in: Neurochemical research Vol. 26; no. 11; pp. 1201 - 1207
• Main Authors: YAMAMOTO, Masahiko, KOBAYASHI, Yasushi, MEI LI, NIWA, Hisayoshi, MITSUMA, Norimasa, ITO, Yasuhiro, MURAMATSU, Tatsuo, SOBUE, Gen
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01-11-2001; Springer Nature B.V
• Subjects: Animals; Animals, Genetically Modified; Biological and medical sciences; Cell Line; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Electroporation; Genetic Therapy - methods; Glial Cell Line-Derived Neurotrophic Factor; Humans; Medical sciences; Mice; Motor Activity - physiology; Motor Neuron Disease - enzymology; Motor Neuron Disease - genetics; Motor Neuron Disease - physiopathology; Motor Neurons - pathology; Muscle, Skeletal - physiology; Nerve Growth Factors; Nerve Tissue Proteins - administration & dosage; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - pharmacology; Neurology; Spinal Cord - pathology; Superoxide Dismutase - genetics; Transfection; Nervous system diseases; Enzyme; Rodentia; Electroporation; Amyotrophic lateral sclerosis; Superoxide dismutase; Striated muscle; Genetic disease; Neurotrophic factor; Vertebrata; Mammalia; Gene; Mouse; Animal; Central nervous system disease; Glial cell line derived neurotrophic factor; Degenerative disease; Oxidoreductases; Mutation; Gene therapy; Spinal cord disease
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1023/A:1013959121424

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.