A non-invasive transport system for GDNF across the blood-brain barrier

Neuroreport. 1997 Jul 7;8(9-10):2293-8. doi: 10.1097/00001756-199707070-00039.

Abstract

Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophin which supports midbrain dopaminergic neurons and spinal cord motorneurons. GDNF has been proposed as a possible therapeutic agent for Parkinson's disease, spinal cord injury or motorneuron degenerative disorders. Administration of GDNF is complicated by its poor penetration across the blood-brain barrier (BBB). Central nervous system capillaries are uniquely enriched in transferrin receptors and antibodies to these receptors (OX-26) have been proposed as potential carriers to transport large molecules across the BBB. Intravenous administration of an OX-26-GDNF conjugate enhanced survival of spinal cord motorneurons in intraocular transplants, which possess an organotypic BBB. This suggests that the OX-26-GDNF conjugate could be utilized for non-invasive treatment of neurodegenerative diseases of the spinal cord or midbrain dopaminergic neurons.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood-Brain Barrier / physiology*
  • Cell Count / drug effects
  • Cell Line
  • Eye / transplantation
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors*
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / pharmacology
  • Neuroprotective Agents / metabolism*
  • Rats
  • Rats, Inbred F344
  • Spinal Cord / transplantation

Substances

  • Gdnf protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Neuroprotective Agents