Pharmacological actions of nerve growth factor-transferrin conjugate on the central nervous system.

Transferrin (Tf) undergoes receptor-mediated transport through the blood-brain barrier in vivo. This property allows transferrin to act as a vector for drug transport to the brain. The present investigation examines both the profile of brain delivery of nerve growth factor (NGF)-transferrin conjugate, and its therapeutic effects on CNS neurodegeneration, which affect locomotion and memory. Delivery of NGF-Tf conjugate to the brain was measured and found to be 0.075% of the injected dose per gram of brain, which is 5-fold higher than that of biotin-NGF. The increased delivery using the NGF-Tf conjugate can be attributed to an increased BBB permeability surface area product, which is about 8-fold higher than that of biotin-NGF. Intravenous injection of biotin-NGF/Tf-avidin conjugate significantly increased neuronal survival in the substantia nigra of a Parkinson's disease mouse model. In addition, this conjugate also improved recognition and memory in Alzheimer's disease rat model. In summary, these results demonstrate that using transferrin as a delivery vector is effective in targeting NGF to the central nervous system (CNS), and may optimize the therapy of age-related neurodegenerative diseases.