Striatal implantation of GDNF releasing biodegradable microspheres promotes recovery of motor function in a partial model of Parkinson's disease.
The recent identification of neurotrophic factors, such as the glial cell line derived neurotrophic factor (GDNF), acting on mesencephalic dopaminergic neurons, offers the possibility to stimulate the axonal regeneration of these cells which are affected in Parkinson's disease. Nevertheless, a safe and efficient GDNF delivery system that may be used in clinical trials is still lacking. We have developed GDNF-releasing microspheres capable of releasing the neurotrophic factor for at least 2 months in vivo. In this study we demonstrate that these microspheres, when implanted in the brains of 'Parkinsonian' rats, were well tolerated, and were able to induce sprouting of the preserved dopaminergic fibers with synaptogenesis. Moreover, this neural regeneration was accompanied by functional improvement. The implantation of GDNF-releasing microspheres could be a promising strategy in the treatment of Parkinson's disease.
Jollivet
Christophe
C
INSERM ERIT-M 0104, Bâtiment IBT, 10 rue Andre Boquel, 49100 Angers, France.
Aubert-Pouessel
Anne
A
Clavreul
Anne
A
Venier-Julienne
Marie Claire
MC
Remy
Séverine
S
Montero-Menei
Claudia N
CN
Benoit
Jean Pierre
JP
Menei
Philippe
P
D020341:Absorbable Implants; D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003342:Corpus Striatum / Q000187:drug effects* / Q000601:surgery; D004337:Drug Carriers / Q000737:chemistry*; D004343:Drug Implants / Q000737:chemistry*; D005240:Feasibility Studies; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008863:Microspheres; D009414:Nerve Growth Factors / Q000008:administration & dosage*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000175:diagnosis* / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D004343:Drug Implants; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D016627:Oxidopamine