Brain BDNF Delivery for Targeting Alzheimer's Disease

Victor Yang, PhD University of Michigan

Project Details

Alzheimer's disease (AD) is characterized by the progressive loss of neurons. Today there is virtually no promising treatment for AD. The primary reason for the lack of effective AD treatment lies in the fact that the brain represents the most difficult territory for pharmacological intervention. The brain possesses the least permeable, so-called blood-brain barrier (BBB), which can block the passage of water-based compounds and virtually all drugs with a high molecular weight. Therefore, despite the recent discovery that brain-derived neurotrophic factors (BDNF) could promote neuronal survival, stimulate their growth, and promote the development of nerve fibers in vitro, they nevertheless could not be applied to AD treatment, because of a lack of a means to deliver these growth factors into the brain. Therefore, the need for an effective delivery system that could deliver a therapeutic level of drugs to the brain for the treatment of AD is imperative. In this project, the researchers are using a clinically approved, biocompartible and biodegradable magnetic resonance imaging agent, the superparamagnetic iron oxide nanoparticles (MION), as a drug carrier. A magnetic field is being used as a tool for specific brain targeting, and the unmatched cell-translocation ability of TAT (the protein transduction domain of the HIV virus) is being used as the means to overcome the BBB. It is hoped that this technique will allow doctors to deliver therapeutic concentrations of BDNF directly into the brain.