Project Grant R61NS137824

Award Date 9/19/24
Completion Date 2/28/27
Dollars Obligated $656K
Funding Federal Agency
National Institute on Aging
Federal Grant Program
93.866
Assistance Type
Project Grant
Place of Performance
Denver, CO 80208, USA
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This $7,704,350 project grant awarded by the National Institute on Aging (CFDA 93.866 - Aging Research) aims to investigate the mechanisms underlying heterogeneity in cognitive outcomes among individuals with Lewy body disorders (LBD), which include Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease with Lewy bodies. The grant will fund four synergistic research projects focused on: 1) the interplay of alpha-synuclein with amyloid and tau pathologies, 2) characterizing human...
This $1,707,089 Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) will fund research by Northwestern University to investigate synergistic approaches for enhancing endoplasmic reticulum (ER) proteostasis, protein trafficking, and lysosomal activity as potential treatments for dementia with Lewy bodies and Parkinson's disease-dementia. The research will use patient-derived induced pluripotent stem cell neuron models and mouse models to test the effects of...
This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) federal grant program, provides $2,234,905.00 in funding to The University of Iowa to support research aimed at understanding the underlying mechanisms responsible for cognitive fluctuations in Lewy body disorders (LBD). The project will use mouse models to evaluate how the accumulation of...
This federal Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) provides $325,779 to the University of Rochester to identify dimensions of Lewy-body dementia (LBD) caregiving, adapt and co-design a peer-led intervention for LBD caregivers, and assess the feasibility and acceptability of the pilot intervention. The award aims to improve holistic support for caregivers of individuals with LBD, which is a neurodegenerative illness and the most common of the...
This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) provides $444,890 to The Regents of the University of California, San Francisco to explore the mechanisms behind the selective spreading of different protein conformations associated with Alzheimer's disease (AD) and Lewy body dementia (LBD). The researchers will utilize mathematical modeling and in vivo mouse studies to identify key genes that mediate the transmission of pathological tau and...
This three-year, $4.766 million project grant from the National Institute on Aging, part of the Department of Health and Human Services, aims to clarify the neuropathological, molecular, and genetic differences between Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) through the Aging Research grant program (CFDA 93.866). The J. David Gladstone Institutes will use digital pathology, artificial intelligence, single-nuclei RNA sequencing, and spatial transcriptomics on...
This $2,069,215 Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) supports research by Case Western Reserve University to investigate the role of the beta-arrestin2-LMBRD2 pathway in the transmission and toxicity of pathological alpha-synuclein, which is a defining hallmark of Lewy body diseases such as Parkinson's disease and dementia with Lewy bodies. The research will utilize cellular and animal models to study the mechanisms by which beta-arrestin2...
This $2,768,769 Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) supports research to investigate the influence of the GBA1 gene on the regulation, trafficking, and maturation of key lysosomal proteins involved in the metabolism of alpha-synuclein. The research will use wildtype and isogenic iPSC-derived neurons to examine how GBA1 mutations affect alpha-synuclein degradation, neuronal release, and the accumulation of alpha-synuclein species found in Lewy...
This federal Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) aims to investigate the interaction between a-synucleinopathies, including dementia with Lewy bodies, Parkinson's disease with dementia, and Alzheimer's disease with Lewy body dementia, and T-cell immunity in Alzheimer's disease and related dementias (ADRD). The $1,669,370 award, provided by the Department of Health and Human Services, will fund an interdisciplinary research effort to examine the...
This federal Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) in the amount of $457,875 will support the development and characterization of the first LRP10 knockout mouse model to investigate the role of LRP10 in the pathogenesis of Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB). The award, with a project period from May 1, 2025 to April 30, 2027, will enable the University of Connecticut Health Center...

This federal Project Grant award from the National Institute on Aging's Aging Research program (CFDA 93.866) provides $655,638 to the University of Denver to develop and test synthetic protein mimetics as potential therapeutics for Lewy body dementia (LBD). The key products and services being delivered under this 2.5-year award include:

  1. Optimization and testing of the pharmaceutical properties of oligopyridylamide (OP) synthetic protein mimetics to inhibit alpha-synuclein aggregation and Lewy body formation in cellular, neuronal, and animal models. This will involve evaluating the ADMET (absorption, distribution, metabolism, excretion, toxicity) profiles of the OP compounds.

  2. Testing the ability of the OP compounds to rescue LBD-related cognitive and motor impairments in a mouse model. The project will also characterize the toxicity of potential OP metabolites through metabolic profiling in the mouse model.

The goal is to identify lead OP therapeutic candidates that can effectively inhibit Lewy body pathology and rescue LBD phenotypes, paving the way for further preclinical and clinical development for this devastating neurodegenerative disease that currently lacks curative treatments.

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