Comparative study of GDNF delivery systems for the CNS: polymer rods, encapsulated cells, and lentiviral vectors

J Control Release. 2003 Feb 21;87(1-3):107-15. doi: 10.1016/s0168-3659(02)00353-x.

Abstract

Glial cell line-derived neurotrophic factor (GDNF) holds great promise for the treatment of Parkinson's disease. In humans, its intracerebroventricular administration leads to limiting side effects. Direct parenchymal delivery using mechanical means, or cell and gene therapy represent potential alternatives. In the present study, a representative of each of these three approaches, i.e. polymer rods, genetically modified encapsulated cells and lentiviral vectors was analyzed for its ability to release GDNF in the striatum of rats. One week post-surgery, GDNF was detected over a distance of 4 mm with all three methods. At 4 weeks GDNF staining diminished with rods and to a lesser extent with encapsulated cells, whereas it increased with lentiviral vectors. Nanogram range of GDNF was measured with all methods at 1 week. At 4 weeks, GDNF levels decreased significantly with rods, whereas they remained stable with encapsulated cells and lentiviral vectors. We conclude that all three methods investigated allow striatal delivery of GDNF, but the time during which it needs to be released will determine the approach chosen for clinical application.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Drug Delivery Systems / methods*
  • Female
  • Genetic Vectors / administration & dosage*
  • Genetic Vectors / pharmacokinetics
  • Glial Cell Line-Derived Neurotrophic Factor
  • Lentivirus
  • Nerve Growth Factors / administration & dosage*
  • Nerve Growth Factors / pharmacokinetics
  • Polymers / administration & dosage*
  • Polymers / pharmacokinetics
  • Rats

Substances

  • Gdnf protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Polymers