Breakthrough in Treating Alzheimer’s Using Targeted Drug Delivery Reported in New England Journal of Medicine

WVU Rockefeller Neuroscience Institute achieves greater reduction in brain amyloid plaques by combining focused ultrasound with antibody treatment

MORGANTOWN, W. Va.–(BUSINESS WIRE)–A potential advancement in the treatment of Alzheimer’s disease was announced today by researchers at the West Virginia University Rockefeller Neuroscience Institute (RNI). A first in-human study, featured in the latest issue of the New England Journal of Medicine, demonstrates that focused ultrasound in combination with anti-amyloid-beta monoclonal antibody treatment can accelerate the clearance of amyloid-beta plaques in the brains of patients with Alzheimer’s disease.

Anti-amyloid-beta (Aβ) monoclonal antibody therapies, such as aduncaumab, lecanemab, and donanemab, can reduce amyloid-beta plaques and slow the progression of Alzheimer’s. Until now, these promising antibody therapies had limitations in reaching the brain due to the blood-brain barrier (BBB), a protective barrier between blood vessels and the brain that blocks harmful substances from getting into the brain, but also limits the access of therapeutics. More than 98 percent of drugs do not readily cross the BBB, thus requiring systemic treatments with higher doses and more frequent therapies.

RNI scientists used a focused ultrasound (FUS) system developed by Insightec to safely and temporarily open the BBB to allow the anti-amyloid-beta antibodies increased access to targeted areas of the brain. The FUS MRI-guided treatment helmet with more than 1,000 ultrasound transducers were directed to specific brain regions with high amyloid-beta plaques.

In this first-in-human proof-of-concept study, three patients (two male and one female, aged 59-77) with mild Alzheimer’s disease received six standard monthly infusions of aducanumab antibody, immediately followed by FUS-mediated BBB opening in regions with high amyloid-beta plaques. The results demonstrated the safety of this approach and increased reduction of amyloid-beta plaques measured by PET scans.

“After six months of antibody treatment, we observed an average of 32 percent more reduction in amyloid-beta plaques (53 percent centiloid) in brain areas with blood-brain barrier opening compared to areas with no such opening,” Ali Rezai, M.D., lead author of the study and executive chair of the RNI, said. “Focused ultrasound is a non-invasive outpatient procedure for BBB opening with great promise for improving drug delivery to the brain.”

“The next phase of the clinical trial will begin this year to explore how to further accelerate amyloid-beta removal in a shorter time with focused ultrasound in combination with lecanemab antibody”, according to Dr. Rezai.

“This is an exciting time in the treatment of Alzheimer’s disease,” Marc Haut, Ph.D., director of the RNI Memory Health Clinic, said. “We are hopeful that the work we are doing may lead to improvements in outcome for many other patients and their families coping with Alzheimer’s.”

About the West Virginia University Rockefeller Neuroscience Institute

The WVU Rockefeller Neuroscience Institute (RNI) is a comprehensive multidisciplinary patient care, education, and research institute providing neurological and mental healthcare for 275,000 patients annually. The 250 physicians and scientists of the RNI improve lives by pioneering advances in neuroscience, brain health, and therapeutics. The RNI team uses the latest technologies with academic, government, and industry partners to make tangible progress to combat public health challenges ranging from addiction to Alzheimer’s disease. For more information about the WVU Rockefeller Neuroscience Institute, visit WVUMedicine.org/RNI.

Reporters: Images and video are available for download at FUS_AD_NEJM_EPK.

Photo captions:

FUS MRI suite.jpg: The focused ultrasound helmet unit with 1,024 ultrasound transducers attaches to the MRI table for MRI-guided treatment.

FUS_MRI_1.jpg: An Alzheimer’s patient undergoes focused ultrasound treatment with the WVU RNI team.

FUS_control_room.jpg: The WVU RNI team, shown in the MRI suite’s control area, plans ultrasound blood-brain barrier treatment.

FUS_illustration.jpg: This illustration of the MRI-guided focused ultrasound system includes a representation of treatment delivery, the target region, and the corresponding opening of the blood-brain barrier demonstrated by contrast enhancement.

LIFU_targeting.png: This 3-D illustration shows how ultrasound waves from inside the helmet converge on a focal point on the brain used for blood-brain barrier opening.

Video: 3-D animation of focused ultrasound procedure for blood-brain barrier opening in conjunction with antibody treatment.

Contacts

Leigh Limerick, RNI Manager of Marketing and Communications, 304-285-8976, [email protected]