期刊
EXPERIMENTAL NEUROLOGY
卷 211, 期 1, 页码 252-258出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2008.01.026
关键词
associated adenoviral vector (AAV); dopamine; fetal tissue; glial derived neurotrophic factor (GDNF); graft; monkey; MPTP; Parkinson's disease; striatum; transplantation
资金
- NINDS NIH HHS [P01 NS044281-01A1, NS 40822, R01 NS040822-03, R55 NS040822, R01 NS040822-01A1, R01 NS040822, P01 NS044281, NS 44281, P01 NS044281-05] Funding Source: Medline
Neural transplantation offers the potential of treating Parkinson's disease by grafting fetal dopamine neurons to depleted regions of the brain. However. clinical studies of neural grafting in Parkinson's disease have produced only modest improvements. One of the main reasons for this is the low survival rate of transplanted neurons. The inadequate supply of critical neurotrophic factors in the adult brain is likely to be a major cause of early cell death and restricted outgrowth of fetal grafts placed into the mature striatum. Glial derived neurotrophic factor (GDNF) is a potent neurotrophic factor that is crucial to the survival, outgrowth and maintenance of dopamine neurons, and so is a candidate for protecting grafted fetal dopamine neurons in the adult brain. We found that implantation of adeno-associated virus type 2 encoding GDNF (AAV2-GDNF) in the normal monkey caudate nucleus induced overexpression of GDNF that persisted for at least 6 months after injection. In a 6-month within-animal controlled study, AAV2-GDNF enhanced the survival of fetal dopamine neurons by 4-fold, and increased the outgrowth of grafted fetal dopamine neurons by almost 3-fold in the caudate nucleus of MPTP-treated monkeys, compared with control grafts in the other caudate nucleus. Thus, the addition of GDNF gene therapy to neural transplantation may be a useful strategy to improve treatment for Parkinson's disease. (C) 2008 Elsevier Inc. All rights reserved.
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