Design and Development of a Full-Ultrasound Phased Array Cns Gene Delivery System( I )

Parkinson's disease (PD) is a chronic degenerative diseases of the CNS system, its etiology is currently speculation and rapid degradation of brain cells in basal ganglia and substantia nigra of the brain which causes dysfunction to produce sufficient nerve transmitter (Dopamine). Current therapeutic approaches include drug (Levodopa) as well as a number of invasive surgical treatments such as pallidotomy, thalamotomy, or deep brain stimulation (DBS), but all only transient symptom relieve. One current treatment is gene therapy, which locally delivers therapeutic/ neurotrophic gene into the brain and has potential for inducing long-term curative effects. Unfortunately, since the presence of the blood-brain barrier (BBB) that block the penetration of gene from circulation to the brain, current gene delivery requires local invasive targeted gene transcranial injection. Focused ultrasound (FUS) with the presence of microbubbles has been shown to temporarily opening the blood-brain barrier, and has been proofed to be able to deliver substance ranging from 70 to 2000kDa into the brain, therefore has high opportunity to be a novel non-invasive brain drug delivery technology. Based on our previous system design experience, we aim to proposed to implement a novel full-mode (transmit mode/ receive mode) focused ultrasound phased array system which is capable to noninvasively deliver therapeutic gene into the brain for PD treatment. Subproject 1 aims to develop a full transmit/receive mode FUS phased array system that can be applied for large-animal targeted gene delivery. Subproject 2 aims to develop novel microbubbles that capable of triggering the BBB-opened effect and concurrently serves as a gene-carrying platform. Subproject 3 aims to establish the PD animal model for small and large animals, safety assessment, and to setup a platform to assess therapeutic efficacy as a reference for future clinical trial. The potential outcomes includes the scientific progress, key technology and IP production, as well as personnel training for medical device or biological industries.

Project ID:PB10507-2952
External Project ID:MOST105-2221-E182-022