Safety and efficacy of focused ultrasound induced blood-brain barrier opening, an integrative review of animal and human studies.

Authors: Meng Y, Pople CB, Lea-Banks H, Abrahao A, Davidson B, Suppiah S, Vecchio LM, Samuel N, Mahmud F, Hynynen K, Hamani C, Lipsman N

The blood-brain barrier, while fundamental in maintaining homeostasis in the central nervous system, is a bottleneck to achieving efficacy for numerous therapeutics. Improved brain penetration is also desirable for reduced dose, cost, and systemic side effects. Transient disruption of the blood-brain barrier with focused ultrasound (FUS) can facilitate drug delivery noninvasively with precise spatial and temporal specificity. FUS technology is transcranial and effective without further drug modifications, key advantages that will accelerate adoption and translation of existing therapeutic pipelines. In this review, we performed a comprehensive literature search to build a database and provide a synthesis of ultrasound parameters and drug characteristics that influence the safety and efficacy profile of FUS to enhance drug delivery.

Introduction

Purpose Drug delivery with BBB opening

Study Objective To review and integrate evidence on the safety and efficacy of focused ultrasound–induced blood–brain barrier opening in animal and human studies.

Cargo name and characteristics Various cargos across reviewed studies: viral vectors (AAV and other gene therapy vectors), proteins/antibodies (monoclonal antibodies, enzymes), small-molecule drugs (including chemotherapeutics and neuroactive agents), nanoparticles (liposomes, polymeric and inorganic nanoparticles), and cell/biologic therapies

Safety and efficacy of focused ultrasound induced blood-brain barrier opening, an integrative review of animal and human studies.

Introduction

Outcomes and Safety

Brain Region

Ultrasound Parameters