Abstract
The trigeminal sensory system was evaluated for the retrograde transfer of gene therapy vectors into the CNS. The feline immunodeficiency viral vector, FIV(HEXB), encoding for the human HEXB gene, was injected intra-articularly in the temporomandibular joint of 12 week-old HexB(-/-) mice displaying clinical and histopathological signs of Sandhoff disease. This treatment regiment reduced GM(2) storage and ameliorated neuroinflammation in the brain of HexB(-/-) mice, as well as attenuated behavioral deficits. In conclusion, retrograde transfer along trigeminal sensory nerves may prove to be a valuable route of gene therapy administration for the treatment of lysosomal storage disorders and other neurodegenerative diseases.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Axonal Transport / genetics
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Behavior, Animal / physiology
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Disease Models, Animal
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Encephalitis / genetics
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Encephalitis / therapy
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G(M2) Ganglioside / genetics
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G(M2) Ganglioside / metabolism
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Genetic Therapy / methods*
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Genetic Vectors / genetics
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Humans
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Immunodeficiency Virus, Feline / genetics
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Lysosomal Storage Diseases, Nervous System / genetics
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Lysosomal Storage Diseases, Nervous System / therapy*
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Mice
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Mice, Knockout
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Neurodegenerative Diseases / genetics
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Neurodegenerative Diseases / therapy*
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Sandhoff Disease / genetics
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Sandhoff Disease / therapy
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Treatment Outcome
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Trigeminal Nerve / cytology
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Trigeminal Nerve / metabolism*
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beta-Hexosaminidase beta Chain / genetics*
Substances
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G(M2) Ganglioside
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HEXB protein, human
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beta-Hexosaminidase beta Chain