Adenovirus vectors for the transfer of foreign genes into cells of the central nervous system particularly in brain

A recombinantly modified nonhuman mammal having central nervous system cells infected with a replication-deficient adenovirus vector comprising a gene under the control of promoter, wherein said gene has been expressed in the nervous system cells of said mammal, and said gene encodes a polypeptide molecule functioning in said cells as a neurotransmitter-synthesizing enzyme, a trophic factor, a neurotrophic factor, a growth factor, nerve growth factor or a lysosomal enzyme, or wherein said gene is an antisense sequence, the transcription product of which blocks the expression of proteins responsible for neuropsychiatric disease, of enzymes involved in the biosynthesis of said proteins or in the biosynthesis of glutamate.

A method for treating Parkinson's Disease which method comprises stereotactically administering to the brain of a mammal suffering from Parkinson's Disease a pharmaceutical composition comprising a replication-defective adenovirus which infects central nervous system cells of said mammal and expressing a nucleotide sequence, contained in said adenovirus, which nucleotide sequence encodes a neurotransmitter-synthesizing enzyme whereby said subject is treated for Parkinson's disease.

A method for expressing a gene in mammalian central nervous system cells, comprising modifying said cells to contain a replication-deficient recombinant adenovirus comprising said gene under the control of a promoter, wherein said gene is an antisense sequence, the transcription product of which blocks the expression in said cells of b-amyloid, b-amyloid precursor or TAU;

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• wherein the gene is expressed in said modified cells.

A recombinantly modified nonhuman mammal having central nervous system cells infected with a replication-deficient adenovirus vector comprising a gene under the control of promoter, wherein said gene has been expressed in the nervous system cells of said mammal, and said gene is an antisense sequence, the transcription product of which blocks the expression of b-amyloid, b-amyloid precursor or TAU.

An ex vivo population of central nervous system cells comprising a replication-defective adenovirus, wherein said adenovirus comprises a nucleotide sequence operably linked to a promoter, wherein said nucleotide sequence encodes a polypeptide molecule functioning in said cells as a neurotransmitter-synthesizing enzyme, a trophic factor, a growth factor, or a lysosomal enzyme.

A process for producing a protein or polypeptide comprising culturing central nervous system cells comprising a replication defective adenovirus, wherein said adenovirus comprises a nucleotide sequence encoding said protein or polypeptide and operably linked to a promoter, wherein said protein or polypeptide is a neurotransmitter-synthesizing enzyme, a trophic factor, a growth factor, or a lysosomal enzyme.

A population of central nervous system cells disposed in a nonhuman animal comprising a replication-defective adenovirus, wherein said adenovirus comprises a nucleotide sequence operably linked to a promoter, wherein said nucleotide sequence encodes a polypeptide molecule functioning in said cells as a neurotransmitter-synthesizing enzyme, a trophic factor, a growth factor, or a lysosomal enzyme.

An isolated population of human central nervous system cells comprising a replication-defective adenovirus, wherein said adenovirus comprises a nucleotide sequence operably linked to promoter, wherein said nucleotide sequence encodes a polypeptide molecule functioning in said cells as a neurotransmitter-synthesizing enzyme, a trophic factor, a growth factor, or a lysosomal enzyme.