Intravenous Administration of a Transferrin Receptor Antibody-Nerve Growth Factor Conjugate Prevents the Degeneration of Cholinergic Striatal Neurons in a Model of Huntington Disease

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 19; pp. 9077 - 9080
• Main Authors: Kordower, Jeffrey H., Charles, Vinod, Bayer, Robert, Bartus, Raymond T., Putney, Scott, Walus, Lee R., Friden, Phillip M.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 13-09-1994; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Antibodies; Antibodies, Monoclonal - administration & dosage; Blood brain barrier; Brain; Cholinergics; Corpus Striatum - pathology; Disease; Dosage; Huntington Disease - pathology; Huntington Disease - therapy; Immunity (Disease); Intravenous injections; Lesions; Male; Nerve Degeneration; Nerve Growth Factors - administration & dosage; Nervous system; Neurons; Neuroscience; Quinolinic Acid; Rats; Rats, Sprague-Dawley; Receptors, Transferrin; Vehicles
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.19.9077

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.