Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectors.
Glial cell line-derived neurotrophic factor (GDNF) holds great promise for the treatment of Parkinson's disease. In humans, its intracerebroventricular administration leads to limiting side effects. Direct parenchymal delivery using mechanical means, or cell and gene therapy represent potential alternatives. In the present study, a representative of each of these three approaches, i.e. polymer rods, genetically modified encapsulated cells and lentiviral vectors was analyzed for its ability to release GDNF in the striatum of rats. One week post-surgery, GDNF was detected over a distance of 4 mm with all three methods. At 4 weeks GDNF staining diminished with rods and to a lesser extent with encapsulated cells, whereas it increased with lentiviral vectors. Nanogram range of GDNF was measured with all methods at 1 week. At 4 weeks, GDNF levels decreased significantly with rods, whereas they remained stable with encapsulated cells and lentiviral vectors. We conclude that all three methods investigated allow striatal delivery of GDNF, but the time during which it needs to be released will determine the approach chosen for clinical application.
Bensadoun
Jean-Charles
JC
Institute of Neurosciences, Swiss Federal Institute of Technology Lausanne EPFL, CH-1015 Lausanne, Switzerland.
Pereira de Almeida
Luis
L
Fine
Eric G
EG
Tseng
Jack L
JL
Déglon
Nicole
N
Aebischer
Patrick
P
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051100:Glial Cell Line-Derived Neurotrophic Factor; D016086:Lentivirus; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011108:Polymers