Reduced alzheimer's disease progression and neutrophil adhesion via competition using neutrophil-derived or engineered nanoparticles
Ended Project Grant Awarded Last action
- Award ID
- R21NS135390
- Recipient
-
Cornell University UEI G56PUALJ3KT5
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $444,555
Award facts
- Assistance listing
- 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
- Completion date
- Originally
- Place of performance
- Ithaca, NY 14853, USA
Award details come from USAspending.gov.
Description
- Abstract
- Many alzheimer's disease (ad) drugs under development target aggregated amyloid beta (ASS) peptide, but this approach is controversial due to disappointing clinical outcomes. Thus, the need to develop new therapeutic strategies for ad persists. Blood flow in the brain of alzheimer disease patients is substantially decreased as compared to age-matched healthy controls. Recently, intravital imaging with two-photon microscopy showed that blood flow in ad mouse models is reduced because neutrophils plug up capillaries resulting in a small, but impactful number of stalled capillaries. Removing these stalls by interfering with neutrophil adhesion improves blood flow in minutes and also improves performance on tasks involving short term or episodic memory within hours. Although this approach is promising because IT targets blood flow and inflammation, key features of ad unaddressed by amyloid-targeting drugs, IT is currently limited to experimental treatments with limited possibility for clinical translation. Existing experimental approaches interfere with a protein not found in humans, LY6G, or would cause severe compromise of the immune system. This proposal aims to develop a novel strategy based on highly biocompatible neutrophil-derived extracellular vesicles or nanoparticles that specifically target and block neutrophil adhesion sites in the brain to reduce capillary stalls and the associated blood flow deficits. These novel agents are encapsulated in neutrophil membranes that preserve many of the neutrophil functions so possess the same targeting capacity as neutrophils. When injected systemically, these engineered particles compete with neutrophils for binding sites on the brain capillaries, acting to reduce neutrophil arrest. Importantly, the particles are only
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Original award | $444,555 |
Quick answers
Who received award R21NS135390?
R21NS135390 was awarded to Cornell University by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on September 22, 2023.
How much is award R21NS135390 worth?
$444,555 has been obligated on R21NS135390.
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