Intravenous administration of a transferrin receptor antibody-nerve growth factor conjugate prevents the degeneration of cholinergic striatal neurons in a model of Huntington disease.
Intrastriatal injections of quinolinic acid induce a pattern of neuronal degeneration similar to that seen in Huntington disease. In the present study, nerve growth factor (NGF) crossed the blood-brain barrier in a dose-dependent fashion following intravenous infusion when conjugated to an antibody directed against the transferrin receptor (OX-26). Intravenous injections of the OX-26-NGF conjugate selectively prevented the loss of striatal choline acetyltransferase-immunoreactive neurons which normally occurs following quinolinic acid administration relative to control rats receiving vehicle or a nonconjugated mixture of OX-26 and NGF. These data demonstrate that a neurotrophic factor-antibody conjugate can prevent the degeneration of central NGF-responsive neurons following systemic administration.
Kordower
J H
JH
Department of Neurological Sciences, Rush Presbyterian Medical Center, Chicago, IL 60612.
Charles
V
V
Bayer
R
R
Bartus
R T
RT
Putney
S
S
Walus
L R
LR
Friden
P M
PM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D003342:Corpus Striatum / Q000473:pathology*; D006816:Huntington Disease / Q000473:pathology / Q000628:therapy*; D008297:Male; D009410:Nerve Degeneration; D009414:Nerve Growth Factors / Q000008:administration & dosage*; D017378:Quinolinic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin
D000911:Antibodies, Monoclonal; D009414:Nerve Growth Factors; D011990:Receptors, Transferrin; D017378:Quinolinic Acid