Jollivet Christophe, Aubert-Pouessel Anne, Clavreul Anne, Venier-Julienne Marie Claire, Remy Séverine, Montero-Menei Claudia N, Benoit Jean Pierre, Menei Philippe
INSERM ERIT-M 0104, Bâtiment IBT, 10 rue Andre Boquel, 49100 Angers, France.
Biomaterials. 2004 Feb;25(5):933-42. doi: 10.1016/s0142-9612(03)00601-x.
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.
最近发现了神经营养因子,如作用于中脑多巴胺能神经元的胶质细胞系衍生神经营养因子(GDNF),这为刺激帕金森病中受影响的这些细胞的轴突再生提供了可能性。然而,仍缺乏一种可用于临床试验的安全有效的GDNF递送系统。我们已经开发出能够在体内至少2个月释放神经营养因子的GDNF缓释微球。在本研究中,我们证明这些微球植入“帕金森病”大鼠脑内后耐受性良好,并且能够诱导保留的多巴胺能纤维发芽并形成突触。此外,这种神经再生伴随着功能改善。植入GDNF缓释微球可能是治疗帕金森病的一种有前景的策略。