What side effects are associated with this type of intervention?

Monoclonal antibody infusion therapies targeting specific proteins involved in Alzheimer's disease, such as beta-amyloid, can cause side effects including infusion reactions, headaches, and amyloid-related imaging abnormalities (ARIA), which may present as brain swelling or microhemorrhages. The process of opening the blood-brain barrier to enhance drug delivery, as done with the Exablate Model 4000 Type 2 device, may increase the risk of infections, neuroinflammation, and potential damage to brain tissue. Patients undergoing these treatments should be closely monitored for these adverse effects.

What other types of research exist?

Promising novel alternatives for treating Mild Cognitive Impairment in 2024 include: 1) Tau-targeting therapies, such as anti-tau monoclonal antibodies and tau aggregation inhibitors, which aim to reduce tau pathology. 2) Small molecule inhibitors targeting beta-amyloid production or aggregation, such as BACE inhibitors and gamma-secretase modulators. 3) Neuroprotective agents, including drugs that target neuroinflammation (e.g., COX-2 inhibitors) and oxidative stress. 4) Gene therapies aimed at modifying genetic risk factors associated with Alzheimer's disease. 5) Advanced drug delivery systems, such as nanoparticle-based delivery, to enhance the penetration of therapeutic agents across the blood-brain barrier without the need for mechanical disruption.

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Monoclonal Antibodies

Aducanumab + Exablate BBB Disruption for Alzheimer's Disease

Q: What is the mechanism of action of this treatment?

Monoclonal antibody infusion therapy targets specific proteins involved in Alzheimer's disease, such as amyloid-beta (Aβ) oligomers and plaques, to help clear them from the brain and potentially slow disease progression. The Exablate Model 4000 Type 2 device uses focused ultrasound to temporarily open the blood-brain barrier, enhancing the delivery of these therapeutic antibodies to the brain. This combination aims to improve treatment efficacy by ensuring higher drug concentrations reach the affected areas, which is crucial for MCI patients as it offers a targeted approach to addressing the underlying pathology of cognitive decline.

Q: What prior FDA approvals exist?

The FDA has approved several monoclonal antibody therapies targeting amyloid-beta proteins involved in Alzheimer's disease, which are relevant to the treatment of Mild Cognitive Impairment (MCI). Notable examples include aducanumab, which targets amyloid-beta plaques. These therapies aim to reduce amyloid plaque buildup in the brain, potentially slowing disease progression. The Exablate Model 4000 Type 2 device, which opens the blood-brain barrier to enhance drug delivery, is currently being studied in combination with these monoclonal antibodies to improve their efficacy. This innovative approach aims to facilitate better drug penetration into the brain, potentially offering more effective treatment options for patients with MCI and early Alzheimer's disease.

Phase < 1

Recruiting

Led By Ali Rezai, MD, FAANS

Research Sponsored by Ali Rezai

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from baseline, up to 5 year post last treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment for early Alzheimer's disease and mild cognitive impairment. It combines a special drug with a technique to help the drug enter the brain more effectively. The goal is to see if this combination is safe and if it can reduce harmful brain proteins.

Who is the study for?

This trial is for people with mild Alzheimer's or cognitive impairment who can communicate during the procedure, have certain scores on mental and depression scales, a specific type of PET scan result, and a reliable caregiver. It excludes those with significant heart disease, liver issues, bleeding disorders, severe depression risk of suicide, untreated sleep apnea, epilepsy, impaired kidney function or are in another clinical trial.

What is being tested?

The study tests the safety of combining Aduhelm (Aducanumab) infusions with Exablate Model 4000 Type 2 device to open the blood-brain barrier in patients. The goal is to see if this combination is safe and feasible for treating mild Alzheimer's disease or cognitive impairment.

What are the potential side effects?

Potential side effects may include reactions related to opening the blood-brain barrier such as temporary discomfort or pain during treatment. There could also be risks associated with Aducanumab infusion like infusion-related reactions and imaging abnormalities.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from baseline, up to 5 year post last treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from baseline, up to 5 year post last treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and from baseline, up to 5 year post last treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Treatment intervention related adverse events

Treatment intervention related serious adverse events

Secondary study objectives

Beta-Amyloid plaques within the brain

Cognitive performance (ADAS COG 11)

Cognitive performance (MMSE)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Infusion plus Exablate BBBO TreatmentExperimental Treatment3 Interventions

Intravenous infusion of Aducanumab or Lecanemab every 2-4 weeks (per standard of care) followed by blood brain barrier opening by FUS.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Aducanumab

2022

Completed Phase 3

~330

Lecanemab

2020

Completed Phase 3

~3530

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Monoclonal antibody infusion therapy targets specific proteins involved in Alzheimer's disease, such as amyloid-beta (Aβ) oligomers and plaques, to help clear them from the brain and potentially slow disease progression. The Exablate Model 4000 Type 2 device uses focused ultrasound to temporarily open the blood-brain barrier, enhancing the delivery of these therapeutic antibodies to the brain. This combination aims to improve treatment efficacy by ensuring higher drug concentrations reach the affected areas, which is crucial for MCI patients as it offers a targeted approach to addressing the underlying pathology of cognitive decline.

Lessons Learnt from the Second Generation of Anti-Amyloid Monoclonal Antibodies Clinical Trials.