Novel, low-cost focused ultrasound system for BBB disruption for the treatment of neurodegenerative diseases
University of Toronto, Sunnybrook & Women’s College
The overall goal of this proposal is to develop a clinical focused ultrasound device that can induce localized, controlled, and repeated opening of the Blood‐Brain Barrier (BBB) for the treatment of neuro‐degenerative diseases. We now have new methods in our laboratory that would allow us to quickly develop a fully controllable, low‐cost, and portable method for drug delivery into the brain.
We will use our extensive experience in device development to construct a clinical device for BBB opening. The aims are to have a system that allows a precise, repeatable, and controlled energy delivery throughout the brain and to perform the feasibility testing in pre-clinical models. At the end of this research period we will have a method that can be used clinically to open the BBB for therapeutic and diagnostic agents that do not normally penetrate the BBB. This research can have a large transformative impact on diagnosis and treatment of brain disease.
Relevance to the acceleration of the therapeutics for neurodegenerative diseases of aging
The successful development of a low cost, portable device that could open the BBB reversibly and safely for therapeutic delivery would open the door for testing the efficacy of a wide variety of molecular agents for the treatment of Alzheimer’s and Parkinson’s diseases. It has been estimated that approximately 98% of all molecules that could be tested for brain treatments do not penetrate the BBB. Therefore, this method could open a new era for brain treatments.
This work will combine the several novel and innovative developments in our laboratory (either patented or patents pending) to develop a new device that can, in a controlled manner, excite MBs in the brain while monitoring their locations such that consistent and safe BBB opening can be induced. This device is new and will make routine clinical treatments possible.
Final project summary
The objective of this project was to develop an ultrasound device and methods for focal opening of the blood¬¬–brain barrier (BBB) for the treatment of brain diseases and that could be used in clinical studies. Computer simulations were used to design the ultrasound array that could both transmit ultrasound and receive the scattered signals. These designs were used to contract the array. The electronics and controlling software required for driving the array were designed, developed and extensively tested in the laboratory. Finally, experiments of the complete system were conducted using large pre-clinical models to test the controlling methods, system performance and safety. The results indicate that the methods developed could be safely used in future clinical trials.