Encapsulated cell biodelivery of GDNF: A novel clinical strategy for neuroprotection and neuroregeneration in Parkinson's disease?

  • Lindvall O
  • Wahlberg L
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The main pathology underlying disease symptoms in Parkinson's disease (PD) is a progressive degeneration of nigrostriatal dopamine (DA) neurons. No effective disease-modifying treatment currently exists. Glial cell line-derived neurotrophic factor (GDNF) has neuroprotective and neuroregenerative effects and it enhances dopaminergic function in animal models of PD. These findings raise the possibility that intrastriatal administration of GDNF might be developed into a new clinical strategy for functional preservation and restoration also in PD patients. Gene therapy is a novel tool to increase local levels of GDNF. Transplantation of encapsulated, GDNF-secreting cells is one strategy for ex vivo cell-based gene delivery which has the advantage to allow for removal of the cells if untoward effects occur. Here we summarize studies with such cells in animals, and discuss the results from previous trials with GDNF in PD patients and their implications for the further development of neuroprotective/neuroregenerative therapies. Finally, we describe the different scientific and regulatory issues that need to be addressed in order to reach the clinic and start the first trial in patients. ?? 2007 Elsevier Inc. All rights reserved.

Author-supplied keywords

  • Device
  • Encapsulated cell
  • GDNF
  • Gene therapy
  • Parkinson disease

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