Gene therapy is considered a promising approach for the treatment of Parkinson’s disease (PD). Tyrosine hydroxylase (TH) is the primary rate-limiting enzyme for dopamine synthesis in dopaminergic neurons, while dopamine decarboxylase (DDC) and GTP cyclohydrolase 1 (GCH1) are essential and regulatory enzymes that are crucial for supporting efficient dopamine production and secretion. In this study, a recombinant lentivirus overexpressing TH, DDC, and GCH1 genes was constructed and transplanted into the right medial forebrain bundle (MFB) of 6-hydroxydopamine (6-OHDA) induced PD rat models. Behavioral analyses at 4 and 8 weeks post-transplantation demonstrated significant functional recovery in PD rats overexpressing the genes, alleviating Parkinsonian behavioral deficits. Histological studies revealed a notable increase in TH-positive cells in the brains of PD rats overexpressing the genes, with the overexpressed genes being expressed in various cells and promoting dopamine secretion. Western blot and enzyme-linked immunosorbent assay analyses also showed a significant elevation in TH expression in the midbrain proteins and dopamine secretion in the cerebrospinal fluid of PD rats, surpassing half of the levels observed in normal rats. This study confirms the potential of lentivirus-mediated gene transplantation for PD therapy, highlighting the role of overexpressed TH, DDC, and GCH1 genes in the treatment of PD rats.
Chang et al. (Sun,) studied this question.