| abstract |
A genetic construct comprising a promoter operably linked to a first coding sequence, which encodes tyrosine hydroxylase (TH), and a second coding sequence, which encodes GTP cyclohydrolase 1 (GCH1), wherein the second coding 5 sequence is 3’ to the first coding sequence, and the first and second coding sequences are part of a single operon, and wherein the genetic construct does not encode aromatic amino acid decarboxylase (AADC), for use in treating a neurodegenerative disorder in a subject, wherein the construct is delivered to the cerebrospinal fluid (CSF) of the subject. The genetic construct may be administered by injection to the CSF via one or more of a group selected from: the intracerebral ventricle system; the cisterna magna; and between lumbar vertebrae L3/L4, L4/L5 or L5/S1. The neurodegenerative disorder to be treated may be a disease associated with catecholamine dysfunction. The neurodegenerative disorder to be treated may be selected from the group consisting of Parkinson's disease, DOPA responsive dystonia, vascular Parkinsonism, side effects associated with L-DOPA treatment, or L-DOPA induced dyskinesia, preferably Parkinson’s disease. A recombinant vector and a pharmaceutical composition comprising the genetic construct are also disclosed. |