Sustained delivery of GDNF: towards a treatment for Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disease characterized by th e progressive loss of nigral dopaminergic neurons. Although symptomatic the rapies to substitute for the missing neurotransmitter dopamine are efficien t at the early stages of the disease, the goal is to find alternative thera pies which could protect dopaminergic neurons from the degenerative process . We have used two distinct gene therapy approaches to deliver the neuropro tective molecule glial cell line-derived neurotrophic factor (GDNF) in anim al models of the disease: (i) an encapsulated genetically engineered cell l ine releasing GDNF (ex vivo gene therapy): and (ii) a lentiviral vector enc oding the GDNF gene (in vivo gene therapy). Both approaches allowed protect ion of nigral dopaminergic neurons against lesion-induced cell death in rod ent as well as monkey models of PD. Behavioral symptoms were also ameliorat ed in these animals [5,14,29,57]. In addition, co-transplantation of embryo nic dopaminergic neuronal grafts and a GDNF-releasing capsule allowed impro vement of graft survival and differentiation, thereby accelerating behavior al recovery [50]. These results should lead to clinical application in the near future. (C) 2001 Elsevier Science BM All rights reserved.