Non-Invasive Delivery of CNS Gene Therapy Using Focused Ultrasound

Background & Unmet Need

• Gene therapy delivery to the brain is difficult due to the need to cross the blood-brain barrier (BBB)
• Current approaches require the vectors to be introduces through direct injection, which is difficult to monitor and exposes the patient to the risks of invasive surgery
• Use of an osmotic agent such as mannitol enables chemical permeabilization of the BBB but requires systemic administration, precluding targeted delivery
• Administration of MRI-guided focused ultrasound (MRgFUS) has been shown to locally open the BBB, but there is a lack of data demonstrating safe and persistent delivery of therapeutics
• Unmet Need: Non-invasive method for targeted delivery of gene therapy to the brain for the treatment of neurological diseases

Technology Overview

• The Technology: Method for transitory disruption of the BBB and targeted delivery of gene therapy using MRgFUS
• Gene therapy delivery can be further restricted by:
• Encapsulation in vesicles specifically disrupted by FUS
• Addition of a tissue-specific microRNA to silence off-target gene expression
• Sequential vector delivery for selective therapy activation
• PoC Study: Successfully introduced GFP transgene into the brains of live rats, with stable gene expression up to 16 months after treatment
• Gene expression was shown to be limited to target brain regions and did not provoke long-term inflammation

Technology Applications

• Treatment of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease
• Treatment of other CS diseases including major depression
• Treatment of monogenic CNS diseases via gene replacement therapy

Technology Advantages

• Enables targeting of specific brain regions
• Demonstrated stable gene expression over time
• Increased efficiency and safety compared to current delivery methods