January 4, 2024, from the Rockefeller Institute for Neuroscienceali r rezai(first author) and other members inthe new england journal of medicine(New England Journal of Medicine, NEJM) published a study called:“ultrasound blood–brain barrier opening and aducanumab in alzheimer’s disease”Research**.
Magnetic resonance imaging (MRI)-guided low-intensity focused ultrasound has been shown to reversibly open the blood-brain barrier in patients with Alzheimer's disease (Figure 1). Anti-amyloid drugs have shown promise in reducing amyloid deposition in the brain and slowing the progression of Alzheimer's disease.
This article uses aducanumab (an anti-amyloid drug) in combination with this focused ultrasound** to briefly open the blood-brain barrier in patients with Alzheimer's disease**, administer to the patient**, and evaluate its efficacy and safety. This article reveals that amyloid levels were significantly reduced in brain regions that received focused ultrasound** more than in contralateral brain regions that did not receive focused ultrasound**, providing evidence of the effectiveness of the combination**, and the adverse events of the combination**(mainly headache).is less rated.
Study design
In this investigator-initiated, prospective, open-label, single-arm, single-institution, proof-of-concept trial,:The investigators aim to evaluate the safety and feasibility of aducanumab monoclonal antibody in combination with focused ultrasound to open the blood-brain barrier on amyloid removal in Alzheimer's disease.
A total of three patients with Alzheimer's disease diagnosed within one year prior to inclusion who did not receive aducanumab** were included in the study, including one 77-year-old male, one 59-year-old male, and one 64-year-old female. In this study, patients received a total of 6 months of focused ultrasound in combination with aducanumab monoclonal antibody**, followed by monthly aducanumab monotherapy**, and follow-up evaluations including amyloid level outcomes, cognitive outcomes, and safety assessments on fluorine-18 florbetaben positron- emission tomography (PET).
Effectiveness evaluation
The study showed that focused ultrasound opens the blood-brain barrier region(Figure 1).Amyloid levels were lower at week 26 compared to baseline(Figure 2).According to the amyloid-pet centiloid score, patient 1 had amyloid levels from 224 at baseline2 points down to 1152 points, patient No. 2 from 1856 points dropped to 1046 points, patient No. 3 from 2515 points dropped to 849 points.
In contrast, for patients who were not exposed to the homologous contralateral region of focused ultrasound**, amyloid levels were similar at baseline at week 26 follow-up. According to the amyloid-pet centiloid score, patient 1 had an amyloid level of 219 at baseline7 points, 218 at week 261 point;Patient 2 had an amyloid level of 129 at baseline3 points, 135 at week 268 points;Patient 3's amyloid level was 246 at baseline9, 238 at week 264 points.
From baseline to week 26, patient 1 had a 107 more reduction in the centiloid scale score of brain regions that received focused ultrasound** compared to the homologous contralateral region that was not exposed to focused ultrasound**5 points, 2 patients more than 876 points, patient 3 more than 1581 point;In summary, brain regions targeted by focused ultrasound had greater reductions in amyloid levels and were more promising** for Alzheimer's disease than those in the contralateral homologous brain regions that were not exposed to focused ultrasound.
For cognitive, behavioral, neither patient 1 nor patient 2 had neurological, cognitive, or behavioral changes at the last follow-up. On day 30 of the follow-up phase, patient 3's RBANS score showed cognitive decline, but no neurological changes or changes in ADLI scores were observed.
Security assessments
During the follow-up phase (180 days after the last combination**), there was one grade 1 adverse event (passive death idea) but it was not considered relevant to this combination**. In addition, headache was the most common adverse event, with all but one case of moderate headache, all of which were mild, and all of these avatars were resolved after surgery.
Conclusion
This proof-of-concept study shows:Aducanumab monoclonal antibody plus focal focused ultrasound** at six months was associated with a greater reduction in amyloid levels and a lower incidence of adverse events in combination with ** compared with aducanumab** alone compared with contralateral homologous brain regions without focused ultrasound.