# Assessment of ultrasound-facilitated neurotherapeutics in Alzheimer's disease

> **NIH NIH R56** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $784,859

## Abstract

Alzheimer’s disease (AD) kills 1 in 3 seniors (more than breast and prostate
cancer combined), increased by 16% during the covid-19 pandemic in 2020 and
is the costliest condition with an expected $355 billion in healthcare costs in 2021
and $1.1 trillion in 2050. Although some effective treatments are available,
Alzheimer’s remains severely undertreated with several pharmacological
compounds failing in clinical trials and/or practice over the past three decades.
Focused Ultrasound (FUS), in conjunction with microbubbles, remains the sole
technique that can induce localized blood-brain barrier (BBB) opening
noninvasively, selectively and safely. Despite the fact that the technology was
initially intended to open the BBB for drug delivery, our group was the first to
report that BBB opening alone can lead to cognitive amelioration in primates. The
safe BBB opening enabled by FUS can lead to an immune cascade that is in turn
correlated with reduction of cognitive deficits and pathology. Prior to our studies
reported herein, the immunotherapeutic potential of the FUS-mediated BBB
opening was unknown. in this renewal study, we aim to determine 1) the
currently unknown neuroprotective and immunotherapeutic mechanisms of FUS-
mediated BBB opening as well as the duration of the aforementioned effects in
multi-session BBB opening, 2) link cognitive improvement and/or immune
response with synaptic density increase, 3) optimize the clinical FUS system for
accurate hippocampal targeting in humans, 3) assess neuroprotection efficacy in
asymptomatic AD subjects and 4) assess immunotherapeutic efficacy in
symptomatic AD subjects. The underlying hypothesis is thus that FUS-mediated
BBB opening alone leads to neuroprotective and immunotherapeutic with
sustained mnemonic amelioration in AD. The multi-disciplinary team
encompasses all critical specialty areas involved, such as ultrasound engineering
as well as MRI, PET and AD pathology, neuroimmunology, cognitive and
memory testing and mouse model development as they pertain to neuroscience
and neurology. Following the proposed studies, this entirely noninvasive and cost
efficient BBB opening technology will be translated in the clinical routine so as to
harness its clinical potential in the treatment of Alzheimer’s.

## Key facts

- **NIH application ID:** 10932398
- **Project number:** 5R56AG038961-12
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Elisa E. Konofagou
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $784,859
- **Award type:** 5
- **Project period:** 2023-09-21 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932398

## Citation

> US National Institutes of Health, RePORTER application 10932398, Assessment of ultrasound-facilitated neurotherapeutics in Alzheimer's disease (5R56AG038961-12). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10932398. Licensed CC0.

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