[Focused ultrasound as a non-invasive method with therapeutic potential in patients with Alzheimer's disease].
Authors: Kovalenko EA, Makhnovich EV, Osinovskaya NA, Bogolepova AN
Alzheimer's disease (AD) is a common, progressive neurodegenerative disease characterized by abnormal deposition of β-amyloid (Aβ) and hyperphosphorylated tau protein. Despite the fact that biomarkers and methods of treating AD are currently being actively studied, there is still no therapy that can significantly reduce the progression of this disease. Therefore, the search for therapeutic disease-modifying strategies is becoming increasingly popular. One such strategy is the use of focused ultrasound (FUS) under MRI guidance using a contrast agent (microbubbles). Under the influence of low-intensity FUS, the blood-brain barrier (BBB) is temporarily opened, which is the main obstacle to the effective delivery of therapeutic compounds to the brain, imposing dimensional and biochemical restrictions on the passage of molecules. One of the processes associated with AD is BBB dysfunction, and therefore the study of the effects of FUS in patients with AD is of interest. The literature data show the effectiveness of FUS in animal models of AD. The researchers attribute the effectiveness of the method to the fact that exposure to FUS induces the opening of BBB and reduces the number of amyloid plaques. It has also been demonstrated that FUS can facilitate the delivery of therapeutic drugs to the brain. This allows considering FUS as a new non-invasive method of treatment. Further research is needed to assess the effectiveness of this method in patients with AD.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To evaluate focused ultrasound as a non-invasive therapeutic method for patients with Alzheimer's disease.
Disease model
Alzheimer's disease
Targeted brain region(s)
Hippocampus
Outcomes and Safety
Summary of Outcomes
A Phase IIa clinical trial demonstrated that repeated MR-guided FUS-mediated BBB opening in the hippocampus and entorhinal cortex of AD patients is safe and reduces amyloid-β plaque burden.
Duration of biological effect
not reported
Safety-related matter
The procedure was well-tolerated with no serious adverse events, brain hemorrhages, or swelling; BBB opening was confirmed as reversible within 24 hours via MRI.
Brain Region
Ultrasound Parameters
Ultrasound instrument
Exablate Neuro 4000 (Insightec)
FUS Frequency
220 kHz
FUS Intensity
not reported
FUS Pressure
not reported
FUS Mode
not reported
Pulse duration
not reported
Duration of a single FUS session
120 s
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