The effects of the controversial Alzheimer’s drug, aducanumab, were improved by using a low-dose ultrasound to better “open” the blood brain barrier, according to research led by Rockefeller Neuroscience Institute.
Their study was published today in the New England Journal of Medicine. The lead author is Rockefeller’s Ali R. Rezai, MD.
“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,” the researchers wrote.
One of the key challenges of therapeutics in Alzheimer’s disease has been restriction by the blood–brain barrier of the delivery of therapeutic agents to brain tissue. Still, the field has forged ahead.
In 2021, the U.S. Food and Drug Administration (FDA) granted approval to aducanumab (Biogen and Eisai’s Aduhelm), an anti-amyloid antibody for early-stage Alzheimer’s disease, despite a lack of clear clinical evidence the drug’s provided cognitive benefits.
But the drug was priced so high, the cost versus benefit became a major issue. The Centers for Medicare and Medicaid Services (CMS) announced that they would only cover individuals enrolled in clinical trials and will limit coverage of future anti amyloid antibodies.
Then in January of this year, the FDA approved Leqembi (lecanemab-irmb, also from Biogen Eisai) via the Accelerated Approval pathway for the treatment of Alzheimer’s disease. This drug has a noticeable, although not substantial, effect on cognitive function. The latest Phase III results show that lecanemab slowed the rate of cognitive decline by 27% in an 18-month study involving participants experiencing the early stage of Alzheimer’s.
Leqembi is expected to net more than $7B in sales over the next few years, despite its efficacy. Fast behind it is Eli Lilly’s donanimhaber, which is expected to be approved in early 2024. It has similar efficacy to Leqembi.
This is encouraging, but still not what anti-amyloid Alzheimer’s drug developers hope to see. These are, after all, the first drugs that address the disease’s underlying cause. That they are not more effective, has been one of the key frustrations in the field.
The Rockefeller team and collaborators have a new approach: Low-intensity focused ultrasound guided by magnetic resonance imaging (MRI) has been shown to reversibly open the blood–brain barrier in patients with Alzheimer’s disease or other neurologic disorders, including Parkinson’s disease, brain tumors, and amyotrophic lateral sclerosis.
Previous studies of focused ultrasound to regions of the brain, without the use of a therapeutic agent, in patients with Alzheimer’s disease have resulted in modest reductions in the levels of amyloid-beta (Aβ) in those regions. In experimental models, the use of focused ultrasound to open the blood–brain barrier increased the level of aducanumab delivery to targeted brain regions to five to eight times as high as that in the untreated regions of the brain.
Many studies suggest anti-Aβ antibodies can reduce levels of Aβ, how much this slows disease progression is a key question.
