title: Intravenous administration of a transferrin receptor antibody-nerve growth factor conjugate prevents the degeneration of cholinergic striatal neurons in a model of Huntington disease.
abstract: 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.
authors.affiliation: Department of Neurological Sciences, Rush Presbyterian Medical Center, Chicago, IL 60612.
authors.forename: J H
authors.initials: JH
authors.lastname: Kordower
authors.forename: V
authors.initials: V
authors.lastname: Charles
authors.forename: R
authors.initials: R
authors.lastname: Bayer
authors.forename: R T
authors.initials: RT
authors.lastname: Bartus
authors.forename: S
authors.initials: S
authors.lastname: Putney
authors.forename: L R
authors.initials: LR
authors.lastname: Walus
authors.forename: P M
authors.initials: PM
authors.lastname: Friden
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D009414:Nerve Growth Factors; D011990:Receptors, Transferrin; D017378:Quinolinic Acid