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Elacridar: Identification of the Molecular Target Relevant to its Anti-Prion Effects and its Application to Other Protein Misfolding Neurodegenerative Diseases

Award Number: R21NS146741
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2025
PERIOD OF PERFORMANCE END DATE: 09/29/2027

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Elacridar: Identification of the Molecular Target Relevant to its Anti-Prion Effects and its Application to Other Protein Misfolding Neurodegenerative Diseases - Prion diseases, while exceptionally rare, have provided a road map to link many protein misfolding neurodegenerative diseases in profound mechanistic ways including the prion-like spread of pathological protein aggregates from cell-to-cell and the neurotoxicity induced by soluble oligomers of these assemblies. Prion diseases also affect other animals, including model organisms (and immortalized cell lines), making them the only neurodegenerative disease that can be directly studied in laboratory experiments. This unprecedented scenario has allowed for the testing and characterization of small molecule therapeutics under real life conditions. We have recently discovered a novel anti-prion compound, elacridar, and preliminary data suggests that it exerts its effects through activating the lysosome, the organelle responsible for the degradation of unwanted proteins. Because of the central role of lysosomes to protein degradation, we extended these studies to determine that elacridar is also efficacious against misfolded α-synuclein and tau, proteins associated with more common neurodegenerative diseases. In this application, we propose experiments designed to define the mechanism of action whereby elacridar exerts its anti-prion effects through identification of the intracellular site(s) where it accumulates, the accompanying proteomic changes induced by this accumulation, and the identification of the molecular target responsible for these effects. We also propose to further explore the effects of elacridar against pathologically misfolded forms of α-synuclein and tau using assays to monitor their cell-to-cell spread, degradation, and neurotoxicity. We anticipate that the knowledge gained by these investigations will provide novel therapeutic targets for the treatment of neurodegenerative diseases.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	MIDWESTERN UNIVERSITY	19555 N. 59TH AVE ADMINISTRATION BUILDING	GLENDALE	AZ	85308	MARICOPA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/15/2026	NEW	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $386,650 )
2025	2025	MIDWESTERN UNIVERSITY	19555 N. 59TH AVE ADMINISTRATION BUILDING	GLENDALE	AZ	85308	MARICOPA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/21/2025	NEW	$386,650
														Subtotal = $386,650

Grand Total All Awards = $386,650

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Elacridar: Identification of the Molecular Target Relevant to its Anti-Prion Effects and its Application to Other Protein Misfolding Neurodegenerative Diseases

Award Number: R21NS146741

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/30/2025

PERIOD OF PERFORMANCE END DATE: 09/29/2027

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