Open AccessIntravenous administration of a transferrin receptor antibody-nerve growth factor conjugate prevents the degeneration of cholinergic striatal neurons in a model of Huntington disease.
Author(s) -
Jeffrey H. Kordower,
Vinod Charles,
Robert C. Bayer,
Raymond T. Bartus,
Scott D. Putney,
Lee Walus,
Phillip M. Friden
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.19.9077
Subject(s) - quinolinic acid , nerve growth factor , choline acetyltransferase , neurotrophic factors , conjugate , endocrinology , medicine , systemic administration , cholinergic neuron , transferrin , antibody , neurotrophin , huntington's disease , receptor , pharmacology , cholinergic , biology , immunology , disease , biochemistry , in vivo , mathematical analysis , tryptophan , mathematics , microbiology and biotechnology , amino acid
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.