@inproceedings{5db1b7e03e644ecfbc6e1f9b4f213ec2,
title = "Ultrasound delivery of an anti-Aβ therapeutic agent to the brain in a mouse model of Alzheimer's disease",
abstract = "Plaques composed of amyloid-beta (Aβ) peptides represent a pathological hallmark in the brain of patients with Alzheimer's disease. Aβ oligomers are considered cytotoxic and several therapeutic approaches focus on reducing Aβ load in the brain of Alzheimer's patients. The efficacy of most anti-Aβ agents is significantly limited because they do not cross the bloodbrain-barrier. Innovative technologies capable of enhancing the permeability of the blood-brain barrier, thereby allowing entry of therapeutic agents into the brain, show great promise in circumventing this problem. The application of low-intensity focused ultrasound in the presence of an ultrasound contrast agent causes localized and transient permeability of the blood-brain barrier. We demonstrate the value of this technology for the delivery of anti-Aβ antibodies to the brain of TgCRND8 mice, a mouse model of Alzheimer's disease exhibiting Aβ plaques. BAM-10, an anti-Aβ antibody, was injected into the tail vein simultaneously with exposure to MRI-guided, low-intensity focused ultrasound (FUS) to one hemisphere of TgCNRD8 mice. Four hours after treatment, antibodies were detected at significant amounts only in the brain of mice receiving FUS in addition to BAM-10. This data provides a proof-of-concept that FUS allows anti-Aβ therapeutics to efficiently enter the brain and target Aβ plaques. Four days following a single treatment with BAM-10 and MRI-guided FUS, a significant decrease in the number of Aβ plaques on the side of the treated hemisphere was observed in TgCRND8 mice. In conclusion low-intensity, focused ultrasound is effective in delivering Aβ antibodies to the brain. This technology has the potential to enhance current anti-Aβ treatments by allowing increased exposure of amyloid plaques to treatment agents.",
keywords = "Alzheimer's disease, Antibody, Drug delivery, Focused ultrasound, Immunotherapy, Microbubbles, Transgenic mouse model",
author = "Jordao, {Jessica F.} and Ayala-Grosso, {Carlos A.} and Rajiv Chopra and JoAnne McLaurin and Isabelle Aubert and Kullervo Hynynena",
year = "2009",
doi = "10.1063/1.3131464",
language = "English (US)",
isbn = "9780735406506",
series = "AIP Conference Proceedings",
pages = "428--432",
booktitle = "8th International Symposium on Therapeutic Ultrasound",
note = "8th International Symposium on Therapeutic Ultrasound ; Conference date: 10-09-2008 Through 13-09-2008",
}