Abstract
(French)
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To determine if neurturin (NTN), a homolog of glial cell line-derived neurotrophic factor (GDNF), is able to preserve tyrosine hydroxylase immunoreactivity (TH-IR) in a rat model of Parkinson's disease (PD), polymer encapsulated cells genetically engineered to release NTN were implanted near the substantia nigra before a unilateral medial forebrain bundle axotomy. One week later, animals that had received a NTN capsule had a significantly higher percentage of TH-IR cells (51.4%) than animals that had received a capsule containing non-transfected parent cells (16.2% compared to the control side). These results suggest that NTN, like GDNF, might be of therapeutic value for the treatment of PD [Neurturin protects dopaminergic neurons following medial forebrain bundle axotomy; JL Tseng, SL Bruhn, AD Zurn, P Aebischer, NeuroReport 9: 1817-1822 (1998)].
Besides ex vivo gene therapy using encapsulated genetically engineered cells, in vivo gene therapy via recombinant viruses can also be used for the localized delivery of neurotrophic factors in the brain. A retroviral vector derived from lentiviruses has been developped as a gene transfer system. Unlike other retroviruses, it is capable of integrating genetic material into the chromosome of postmitotic cells and does not encode viral proteins. We have used this lentiviral vector for the localized delivery of GDNF in a rat model of PD. Following a single injection in the substantia nigra of adult rats with a vector expressing GDNF, 56% of the nigral dopaminergic neurons remained following medial forebrain bundle axotomy, compared to 24% in animals transduced with a control reporter gene. Lentiviral vectors could thus be useful tools as vectors for the local delivery of bioactive molecules into defined structures of the central nervous system (Self-inactivating lentiviral vectors with enhanced transgene expression as a potential gene transfer system for Parkinson's disease; N. Déglon, JL Tseng, JC Bensadoun, AD Zurn, Y Arsenijevic, L Pereira de Almeida, R Zufferey, D Trono, P Aebischer, submitted for publication).
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