Focused-Ultrasound Brain Gene Delivery for Parkinson's Disease Therapy

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 includes drug treatment (Levodopa), surgical treatment for unilateral globus pallidus Cauterization (Pallidotomy), burning of the subthalamic nucleus (thalamotomy), and deep brain stimulation (deep-brain-stimulation). However, current long-term efficacy of Levodopa is not ideal, surgical treatment is invasive and is still associated with surgical risk such as intracranial hemorrhage, cerebral stroke, infection, or normal nerve fiber damage. One current potential treatment is gene therapy, that is, therapeutic gene such as AADC and GDNF carried by recombinant adeno-associated virus (rAAV) and perform local and direction cranial injection, and current clinical trials have shown considerable success, providing high potential for Parkinson's treatment or progression control. Recently, focused ultrasound 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 technologies. In this research, we aim to explore the use of ultrasound to open the blood-brain barrier and locally deliver therapeutic genes into the brain. We aim to assess whether it can replace the existing local intracranial injection of gene therapy for Parkinson's procedures. This study will be carried out in three years. First-year objective is to assess whether ultrasound can be local delivery of gene and expression in the brain, as well as its performance characteristics analysis, and to characterize and optimize gene expression after perform FUS BBB opening. Based on technical establishment, in year 2, we aim to establish small-animal (mice) PD model, and to evaluate the therapeutic performance of delivering therapeutic genes to treat small-animal PD model. In year 3, we aim to establish large-animal (primate) PD model, and to explore the therapeutic efficacy of the PD model treatment.

Project ID:PB10301-0505
External Project ID:NSC102-2221-E182-020-MY3