A non-invasive transport system for GDNF across the blood-brain barrier.
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.
Albeck
D S
DS
Department of Basic Science, University of Colorado Health Science Center, Denver 80262, USA.
Hoffer
B J
BJ
Quissell
D
D
Sanders
L A
LA
Zerbe
G
G
Granholm
A C
AC
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002452:Cell Count / Q000187:drug effects; D002460:Cell Line; D005123:Eye / Q000637:transplantation; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000637:transplantation
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents