Peripheral Administration of Nerve Growth Factor Conjugated to an Anti-transferrin Receptor Antibody Increases Cholinergic Neuron Survival in Intraocular Forebrain Transplants

Publisher Summary This chapter focuses on peripheral administration of nerve growth factor conjugated to an anti-transferrin receptor antibody. Neurotrophic molecules play a role in the survival and maintenance of some adult central neurons. Nerve growth factor (NGF) was the first trophic factor to be characterized and sequenced. The study presented in this chapter has demonstrated that NGF covalently conjugated to a protein vector delivery system, the OX-26 rat antibody against the transferrin receptor, can be successfully transported across the blood–brain barrier (BBB) in septal grafts in oculo. This antibody–NGF conjugate significantly improves survival of intraocular septal cholinergic neuron transplants for at least 5 months after cessation of treatment. The conjugate does not have any significant effects on other neural or glial structures in the grafts or in the peripheral host adrenal glands. In addition, the conjugate does not seem to stimulate the production of antibodies directed against NGF in the hosts. The levels of NGF in the host cerebellum were significantly increased several hours following a single OX-26–NGF conjugate injection. These data indicate that delivery of large peptide neurotherapeutics such as growth factors into the brain may be possible utilizing the iron–transferrin transport mechanism.