New horizons for focused ultrasound (FUS) - therapeutic applications in neurodegenerative diseases.
Access to the CNS and delivery of therapeutics across the blood-brain barrier remains a challenge for most treatments of major neurological diseases such as AD or PD. Focused ultrasound represents a potential approach for overcoming these barriers to treating AD and PD and perhaps other neurological diseases. Ultrasound (US) is best known for its imaging capabilities of organs in the periphery, but various arrangements of the transducers producing the acoustic signal allow the energy to be precisely focused (F) within the skull. Using FUS in combination with MRI and contrast agents further enhances accuracy by providing clear information on location. Varying the acoustic power allows FUS to be used in applications ranging from imaging, stimulation of brain circuits, to ablation of tissue. In several transgenic mouse models of AD, the use of FUS with microbubbles reduces plaque load and improves cognition and suggests the need to investigate this technology for plaque removal in AD. In PD, FUS is being explored as a way to non-invasively ablate the brain areas responsible for the tremor and dyskinesia associated with the disease, but has yet to be utilized for non-invasive delivery of putative therapeutics. The FUS approach also greatly increases the range of possible CNS therapeutics as it overcomes the issues of BBB penetration. In this review we discuss how the characteristics and various applications of FUS may advance the therapeutics available for treating or preventing neurodegenerative disorders with an emphasis on treating AD and PD.
Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV 26505. Electronic address: dum6@cdc.gov.
Diane B
DB
Miller
Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, WV 26505. Electronic address: jdo5@cdc.gov.
James P
JP
O'Callaghan
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D000818:Animals; D001812:Blood-Brain Barrier; D003287:Contrast Media / Q000009:adverse effects / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000009:adverse effects; D018014:Gene Transfer Techniques / Q000009:adverse effects / Q000639:trends; D006801:Humans; D061185:Mechanical Thrombolysis / Q000009:adverse effects / Q000379:methods / Q000639:trends; D045423:Microbubbles / Q000009:adverse effects / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018697:Nootropic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000639:trends; D009626:Terminology as Topic; D035703:Therapies, Investigational / Q000009:adverse effects / Q000639:trends; D014464:Ultrasonic Therapy / Q000009:adverse effects / Q000639:trends
D003287:Contrast Media; D018696:Neuroprotective Agents; D018697:Nootropic Agents
Microbubbles; Obicodilation; Sonothrombolysis; Transcalvarial FUS; Transcranial