Adenoviral-vector-mediated gene transfer into medullary motor neurons

A method of producing a neurotrophic factor in mammalian motor neurons at a specific medullary stage, said method comprising administering directly to muscle tissue a replication defective adenovirus comprising a nucleic acid encoding said protein, wherein the muscle tissue comprises a nerve linkage with the specific medullary stage, wherein the nucleic acid is operably linked to a promoter, and wherein said nucleic acid is delivered to said motor neurons and expressed in the mammal at the specific medullary stage.

A method of inducing peripheral or collateral sprouting of motor axon endings at a specific medullary stage of a mammal, said method comprising administering directly to muscle tissue a replication defective adenovirus comprising a nucleic acid encoding a neurotrophic factor, wherein the muscle tissue comprises a nerve linkage with the specific medullary stage, wherein the nucleic acid is operably linked to a promoter, and wherein expression of said nucleic acid in the mammal induces peripheral or collateral sprouting of motor axon endings at the specific medullary stage.

A method of protecting against axonal degeneration in an ALS patient comprising administering directly to muscle tissue at a specific medullary stage a replication defective adenovirus comprising a nucleic acid encoding a neurotrophic factor to mammalian muscle tissue, wherein said nucleic acid is delivered to motor neurons at the specific medullary stage and expressed, and the expressed nucleic acid protects said neurons against axonal degeneration by inducing peripheral or collateral sprouting of motor axon endings at the specific medullary stage.

A method of treating an ALS patient comprising administering directly to muscle tissue of the ALS patient a replication defective adenovirus comprising a nucleic acid encoding a neurotrophic factor, wherein the muscle tissue is innervated by a motor neuron located at a specific medullary stage, wherein the nucleic acid is operably linked to a promoter, wherein said nucleic acid in the muscle tissue is delivered to motor neurons of the specific medullary stage and expressed, and wherein expression of the nucleic acid sequence in the ALS patient results in increased innervation of muscle tissue of the same medullary level as the muscle tissue that was administered the nucleic acid, increased peripheral sprouting of motor axon endings, increased collateral sprouting of motor axon endings, extended lifespan, or combinations thereof.

A method of treating amyotrophic lateral sclerosis comprising administering directly to muscle tissue of a specific medullary stage of a mammal suffering there from a replication defective adenovirus comprising a gene encoding neurotrophin-3, wherein the gene is operably linked to a promoter, and wherein expression of the gene in the mammal results in increased innervation of muscle tissue of the same medullary level as the muscle tissue that was administered the gene, increased peripheral sprouting of motor axon endings, increased collateral sprouting of motor axon endings, extended lifespan, or combinations thereof.

A method of delivering a nucleic acid encoding a neurotrophic factor to mammalian motor neurons at a specific medullary functional level comprising administering directly to muscle tissue a replication defective adenovirus comprising said nucleic acid proximate to the site of a nerve linkage associated with the chosen medullary functional level, wherein the nucleic acid is operably linked to a promoter, and wherein said nucleic acid in the muscle tissue is delivered to said motor neurons of the specific medullary functional level.

A method of delivering a nucleic acid encoding an antisense sequence to mammalian motor neurons at a specific medullary stage, said method comprising administering directly to muscle tissue of the specific medullary stage a replication defective adenovirus comprising said nucleic acid, wherein the nucleic acid is operably linked to a promoter, and wherein said nucleic acid in the muscle tissue is delivered to said motor neurons at the specific medullary stage.