This technology makes use of focused ultrasound (FUS) and microbubble technologies to achieve localized, efficient, and non-invasive delivery of therapeutics through the blood brain barrier and into the brain.
Unmet Need: Efficient system for delivering drugs across the blood brain barrier
The brain is shielded by a unique vascular system known as the blood-brain barrier (BBB). While the BBB serves as a defense system to guard the brain from toxins, it also represents a major obstruction to neurological drug delivery for therapeutic applications. Although focused ultrasound (FUS) and microbubbles have been shown to noninvasively and locally deliver large molecules through the BBB to treat neurological diseases such as Alzheimer's disease, Parkinson's disease, and brain cancer, most studies to date have assumed that long pulse lengths (PLs) were necessary for BBB opening, thus restricting the range of modifiable parameters that can improve delivery characteristics.
The Technology: Optimized focused ultrasound pulse sequence for delivery of neuroactive drugs
This technology uses short PLs to open the BBB using a unique burst sequence. This pulse sequence was selected from an array of pulse parameters based on its superior ability to enhance FUS-induced brain molecular delivery characteristics. Drug delivery measurements revealed that short PLs penetrate the skull better than higher frequencies, allowing for better focal disruption of BBB opening. The technology also presents optimal parameters for using FUS to increase the permeability of the BBB to large agents, such as dextran (70 kDa) and lipid microspheres, therefore expanding the parameters for future drug development.
This technique has been tested and shown to be efficacious using in vivo models.
Applications:
- Non-invasive administration of drugs that are delivered via trans-cranial surgery
- Expanding the scope of potential neurological therapeutic small molecules
- Specific drug targeting of neurological disorders with known, focal pathologies
- Cost-effective, quick treatment for a variety of neurological maladies
Advantages:
- Minimally invasive technique
- Safer and more expedient than cranial surgical procedures
- Non-toxic method of BBB penetration
- Allows for highly localized procedure to access specific regions of the brain
- Cost-effective technology
- Extension of FDA approved techniques (MRI, ultrasound, and microbubbles)
- Consistently efficacious for drug delivery into the brain
Lead Inventor:
Elisa Konofagou, Ph.D.
Patent information:
Patent Status
Related Publications:
Pouliopoulos A, Kwon N, Jensen G, Meaney A, Niimi Y, Burgess MT, Ji R, McLuckie AJ, Munoz FA, Mamimura HA, Teich AF, Ferrera VP, Konofagou EE. “Safety evaluation of a clinical focused ultrasound system for neuronavigation guided blood-brain barrier opening in non-human primates” Sci Rep. 2021 Jul 22; 11(1).
Englander ZK, Wei HJ, Pouliopoulos AN, Bendau E, Upadhyayula P, Jan CI, Spinazzi EF, Yoh N, Tazhibi M, McQuillan NM, Wang TJC, Bruce JN, Canoll P, Feldstein NA, Zacharoulis S, Konofagou EE, Wu CC. “Focused ultrasound mediated blood-brain barrier opening is safe and feasible in a murine pontine glioma model” Sci Rep. 2021 Mar 22; 11(1).
Pouliopoulos AN, Jimenez DA, Frank A, Robertson A, Zhang L, Kline-Schoder AR, Bhaskaw V, Harpale M, Caso E, Papapanou N, Anderson R, Li R, Konofagou EE. “Temporal stability of lipid-shelled microbubbles during acoustically-mediated blood-brain barrier opening” Front Phys. 2020 May; 8: 137.
Ji R, Smith M, Niimi Y, Narakatsani ME, Murillo MF, Jackson-Lewis V, Przedborski S, Konofagou EE. “Focused ultrasound enhanced intranasal delivery of brain derived neurotrophic factor produces neurorestorative effects in a Parkinson’s disease mouse model” Sci Rep. 2019 Dec 18; 9(1): 19402.
Chen H, Yang GZX, Getachew H, Acosta C, Sánchez CS, Konofagou EE. “Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor” Sci Rep. 2016 Jun 27; 6: 28599.
Choi JJ, Wang S, Tung YS, Morrison B, Konofagou EE. "Molecules of various pharmacologically-relevant sizes can cross the ultrasound-induced blood-brain barrier opening in vivo" Ultrasound Med Biol. 2010 Jan; 36(1): 58-67.
Tech Ventures Reference:
IR 2781, 2687, 2636, 2039, M09-025
Licensing Contact: Dovina Qu
