Abstract: Provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding TH is linked to the nucleotide sequence encoding CH1 such that they encode a fusion protein TH-CH1. Also provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding AADC is linked to the nucleotide sequence encoding TH such that they encode a fusion protein AADC-TH or TH-AADC. Further provided is a viral vector comprising such nucleotide sequences and its use in the treatment and/or prevention of Parkinson's disease.

Abstract: Provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding TH is linked to the nucleotide sequence encoding CH1 such that they encode a fusion protein TH-CH1. Also provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding AADC is linked to the nucleotide sequence encoding TH such that they encode a fusion protein AADC-TH or TH-AADC. Further provided is a viral vector comprising such nucleotide sequences and its use in the treatment and/or prevention of Parkinson's disease.

Abstract: Provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding TH is linked to the nucleotide sequence encoding CH1 such that they encode a fusion protein TH-CH1. Also provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding AADC is linked to the nucleotide sequence encoding TH such that they encode a fusion protein AADC-TH or TH-AADC. Further provided is a viral vector comprising such nucleotide sequences and its use in the treatment and/or prevention of Parkinson's disease.

Abstract: Provided is a lentiviral vector for delivery to the brain for use in treating a neurological condition, wherein the lentiviral vector is delivered directly to the brain by delivering the lentiviral vector via six or fewer tracts per hemisphere, at a single deposit point per tract.

Abstract: Provided is a lentiviral vector for delivery to the brain for use in treating a neurological condition, wherein the lentiviral vector is delivered directly to the brain by delivering the lentiviral vector via six or fewer tracts per hemisphere, at a single deposit point per tract.

Abstract: Provided is an improved treatment for Parkinson's Disease where the efficacy of L-Dopa treatment is increased by including gene therapy in the treatment regimen. The combination therapy results in long-term improvements in response to L-Dopa and diminished side effects caused by L-Dopa.

Abstract: Provided is a lentiviral vector for delivery to the brain for use in treating a neurological condition, wherein the lentiviral vector is delivered directly to the brain by delivering the lentiviral vector via six or fewer tracts per hemisphere, at a single deposit point per tract.

Abstract: The present invention provides methods for: (i) treating and/or preventing Parkinson's disease in a subject without causing cognitive impairment by using dopamine replacement gene therapy to maintain or restore constant physiological dopaminergic tone in both the dorsal and ventral striatum of the subject; (ii) normalising neuronal electrical activity in basal ganglia and/or subthalamic nucleus in a Parkinson's disease subject; and (iii) treating and/or preventing dyskinesias associated with oral L-dopa administration in a Parkinson's disease subject by administration of a vector system for dopamine replacement gene therapy to the subject.