Microbubble protein delivery for Parkinson’s

Abstract

Microbubbles (MBs) are small (1-5 μm diameter), perfluorcarbon gas filled lipid microspheres used for contrast enhancement during ultrasound imaging. MBs (Definity®, others) are approved for contrast echocardiography and widely used (6 M patient injections) as ultrasound contrast agents with established pharmacokinetics and clearance data. Recent research has shifted to the therapeutic potential of MBs and the NRC and Artenga Inc. developed a novel strategy (Patent to be filed) to load biologics onto MBs with high, consistent loading using a novel clinically scalable methodology. Investigators at Sunnybrook Research Institute have pioneered MR guided focused ultrasound (MRgFUS) plus MB techniques to deliver a wide range of therapeutic agents through the blood-brain-barrier (BBB) and developed a state of the art MRgFUS system for animal models. MRgFUS can precisely target the substantia nigra (SN) and striatum (ST) for simultaneous targeting of multiple brain regions. Neurotrophic factors (NTFs) are being developed in the hope of halting or reversing the progression of neuronal loss in chronic neurodegenerative diseases, however, their clinical utility is limited by drug delivery issues. Recently the University of Helsinki discovered a novel NTF, cerebral dopamine neurotrophic factor (CDNF), with a unique structure and mode of action. CDNF has demonstrated improved efficacy compared to GDNF in various preclinical models of PD. Artenga, Inc., Sunnybrook Research Institute, the National Research Council of Canada (NRC), and the University of Helsinki plan is to use MR guided focused ultrasound (MRgFUS) and neurotrophic drug-loaded microbubbles (NTF-MBs) for targeted, noninvasive, blood brain barrier (BBB) drug delivery of CDNF.