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Principal Investigator: Elisa E. Konofagou
Organization: COLUMBIA UNIVERSITY HEALTH SCIENCES
Fiscal Year: 2024
Award: $784,859
Funding agency: National Institute on Aging
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.
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era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 pandemic><COVID-19 period><COVID-19 public health crisis><COVID-19 years><Central Nervous System Diseases><Central Nervous System Disorders><Clinical><Clinical Trials><Code><Coding System><Cognition><Cognitive><Cognitive deficits><Cornu Ammonis><Degenerative Neurologic Disorders><Dependence><Drug Delivery><Drug Delivery Systems><Encephalon><Engineering><Episodic memory><Focused Ultrasound><Frameless Stereotaxy><Funding><Health Care Costs><Health Costs><Healthcare Costs><Hemato-Encephalic Barrier><Hematologic Tests><Hematological Tests><Hematology Testing><Hippocampus><Hortega cell><Human><Immediate Memory><Immune><Immune Cell Activation><Immune mediated therapy><Immune response><Immunes><Immunological response><Immunologically Directed Therapy><Immunotherapeutic agent><Immunotherapy><Infrastructure><Journals><Link><Longitudinal Studies><MR Imaging><MR Tomography><MRI><MRIs><MT-bound tau><Macrophage><Magazine><Magnetic Resonance Imaging><Malignant Breast Neoplasm><Malignant Tumor of the Prostate><Malignant neoplasm of prostate><Malignant prostatic tumor><Maps><Mediating><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Memory><Memory Deficit><Memory impairment><Mice><Mice Mammals><Microbubbles><Microglia><Modern Man><Monitor><Murine><Mus><Mφ><NMR Imaging><NMR Tomography><National Institute of Aging><National Institute on Aging><Nervous System Degenerative Diseases><Nervous System Diseases><Nervous System Disorder><Neural Degenerative Diseases><Neural degenerative Disorders><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurologic Degenerative Conditions><Neurologic Disorders><Neurological Disorders><Neurology><Neuronavigation><Neurosciences><Nuclear Magnetic Resonance Imaging><Onset of illness><Outcome><PET><PET Scan><PET imaging><PETSCAN><PETT><Pathology><Peer Review><Peripheral><Pharmacological Treatment><Phenotype><Positron Emission 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emitting tomography><post treatment><primary degenerative dementia><recruit><response><senile dementia of the Alzheimer type><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><sex><simulation><soluble amyloid precursor protein><synapse><tau><tau Proteins><tau factor><three dimensional><timeline><transcriptomics><translation><ultrasound><working memory><τ Proteins>