Neuroprotection in a rat Parkinson model by GDNF gene therapy using EIAV vector.
Vectors based on lentiviruses are opening up new approaches for the treatment of neurodegenerative diseases. Currently, the equine infectious anaemia virus (EIAV) vector is one of the most attractive gene delivery systems with respect to neuronal tropism. The aim was to validate EIAV-lentiviral vectors as a gene delivery system for neurotrophic factor genes in an animal model of Parkinson's disease. EIAV carrying the glial cell line-derived neurotrophic factor (GDNF) gene was unilaterally injected into rat striatum and above the substantia nigra (SN). One week later, the rats received a 6-OHDA lesion into the ipsilateral striatum. GDNF delivery led to extensive expression of GDNF protein within the striatum. In addition, near complete protection against dopaminergic cell death was observed in the GDNF-treated group.
Azzouz
Mimoun
M
Oxford BioMedica (UK) Ltd, The Oxford Science Park, Medawar Center, Oxford OX4 4GA, UK.
Ralph
Scott
S
Wong
Liang-Fong
LF
Day
Denise
D
Askham
Zoe
Z
Barber
Robert D
RD
Mitrophanous
Kyriacos A
KA
Kingsman
Susan M
SM
Mazarakis
Nicholas D
ND
D000818:Animals; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D004860:Infectious Anemia Virus, Equine / Q000235:genetics; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000235:genetics / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents