Feasibility of Using MRI-Guided Focused Ultraosund for Neurodegenerative Drug Delivery into the Brain

Alzheimer's disease is a common chronic neurological disorder that is characterized by recurrent unprovoked seizures. These seizures are transient signs and/or symptoms due to abnormal, excessive or synchronous neuronal activity in the brain, and the seizures happen when clusters of nerve cells, or neurons, in the brain send out the wrong signals. Epilepsy has many possible causes, including illness, brain injury and abnormal brain development. In many cases, the cause is unknown. Long-term drug control or surgical operations are the current most common approach for the syndrome control approach. Recently, it has been discovered that focused ultrasound (FUS) can transiently disrupt the blood-brain barrier so that permit the local delivery of macro-molecular therapeutic agent delivery into brain for therapeutic purpose. Recently, it shows exciting advances that using focused ultrasound to regulate BBB permeability promote entry of plasma-derived therapeutic anti-Aβ antibodies into the CNS to clear brain-derived Aβ plagues. The purpose of this application is to propose a focused ultrasound treatment to treat Alzheimer's disease by delivering macro therapeutic Aβ antibodies and verified its feasibility by using animal model. In this study, we intend to combine the technique of drug delivery with focused ultrasound to open the BBB for neurodegenerative drug delivery in an AD animal model. We believe that early treatment with anti-Aβ antibodies delivery enhanced by focused ultrasound will show significant impact than treatment in the irreversible late phase. In the first stage, we aim to develop a MRI-guided FUS system that can perform the local/ reversible BBB opening to facilitate the delivery of anti-Aβ antibodies. In the second stage, we aim to establish Alzheimer’s disease animal model and behavior monitoring system. In the third stage, we aim to test the efficacy of FUS-induced local enhanced delivery of anti-Aβ antibodies facilitate the clearance of Aβ plagues in the brain and bring therapeutic efficacy on the Alzheimer’s disease animal model.

Project ID:PB10107-1740
External Project ID:NSC101-2221-E182-002-MY3