Ultrasound delivery of an anti-Aβ therapeutic agent to the brain in a mouse model of Alzheimer's disease

Jessica F. Jordao, Carlos A. Ayala-Grosso, Rajiv Chopra, JoAnne McLaurin, Isabelle Aubert, Kullervo Hynynena

1 Scopus citations

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.

Original languageEnglish (US)
Title of host publicationAIP Conference Proceedings
Pages428-432
Number of pages5
Volume1113
DOIs
Publication statusPublished - 2009
Event8th International Symposium on Therapeutic Ultrasound - Minneapolis, MN, United States
Duration: Sep 10 2008Sep 13 2008

Other

Other8th International Symposium on Therapeutic Ultrasound
CountryUnited States
CityMinneapolis, MN
Period9/10/089/13/08

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Keywords

  • Alzheimer's disease
  • Antibody
  • Drug delivery
  • Focused ultrasound
  • Immunotherapy
  • Microbubbles
  • Transgenic mouse model

ASJC Scopus subject areas

  • Physics and Astronomy(all)

Cite this

Jordao, J. F., Ayala-Grosso, C. A., Chopra, R., McLaurin, J., Aubert, I., & Hynynena, K. (2009). Ultrasound delivery of an anti-Aβ therapeutic agent to the brain in a mouse model of Alzheimer's disease. In AIP Conference Proceedings (Vol. 1113, pp. 428-432) https://doi.org/10.1063/1.3131464