Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease

Rezai, Ali R. M.D.
D'Haese, Pierre-Francois Ph.D.
Finomore, Victor Ph.D.
Carpenter, Jeffrey M.D.
Ranjan, Manish M.B., B.S.
Wilhelmsen, Kirk M.D.
Mehta, Rashi I. M.D.
Wang, Peng Ph.D.
Najib, Umer M.D.
Teixeira, Camila Vieira Ligo Ph.D.
Arsiwala, Tasneem Ph.D.
Tarabishy, Abdul M.D.
Tirumalai, Padmashree Ph.D.
Claassen, Daniel O. M.D.
Hodder, Sally M.D.
Haut, Marc W. Ph.D.

From the Departments of Neurosurgery (A.R.R., P.-F.D., M.R.), Neuroradiology (P.-F.D., J.C., R.I.M., P.W., A.T.), Neuroscience (A.R.R., V.F., C.V.L.T., T.A., P.T., M.W.H., R.I.M.), Neurology (K.W., U.N., M.W.H.), and Behavioral Medicine and Psychiatry (M.W.H.), Rockefeller Neuroscience Institute, Department of Medicine (S.H.), and West Virginia Clinical and Translational Science Institute (S.H.), West Virginia University, Morgantown; and the Department of Neurology, Vanderbilt University, Nashville (D.O.C.).

Dr. Rezai can be contacted at [email protected] or at the Rockefeller Neuroscience Institute, West Virginia University, 33 Medical Center Dr., Morgantown, WV 26506.

Supported by a grant from the Harry T. Mangurian, Jr. Foundation, and internal research funds from the West Virginia University Rockefeller Neuroscience Institute.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

New England Journal of Medicine 390(1):p 55-62, January 4, 2024. | DOI: 10.1056/NEJMoa2308719

SUMMARY

Antiamyloid antibodies have been used to reduce cerebral amyloid-beta (Aβ) load in patients with Alzheimer's disease. We applied focused ultrasound with each of six monthly aducanumab infusions to temporarily open the blood-brain barrier with the goal of enhancing amyloid removal in selected brain regions in three participants over a period of 6 months. The reduction in the level of Aβ was numerically greater in regions treated with focused ultrasound than in the homologous regions in the contralateral hemisphere that were not treated with focused ultrasound, as measured by fluorine-18 florbetaben positron-emission tomography. Cognitive tests and safety evaluations were conducted over a period of 30 to 180 days after treatment. (Funded by the Harry T. Mangurian, Jr. Foundation and the West Virginia University Rockefeller Neuroscience Institute.)

Ultrasound to Open Blood-Brain Barrier with Aducanumab

In three patients with Alzheimer's disease, focused ultrasound was applied with aducanumab therapy. Reduction in amyloid was greater in treated regions than in matched contralateral regions over 6 months.

Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease

SUMMARY

Ultrasound to Open Blood-Brain Barrier with Aducanumab

Corresponding Article

Sounding Out the Blood-Brain Barrier