Sunday, May 11, 2025 5/11/2025

Development of autophagy modulators for evaluation as a therapeutic strategy for Niemann-Pick Type C

Award Number: R01NS114413
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Description

Development of autophagy modulators for evaluation as a therapeutic strategy for Niemann-Pick Type C - Autophagy is a cellular homeostasis pathway that has been implicated in numerous diseases. One of these diseases, Niemann-Pick disease type C (NPC), is an autosomal recessive, neurodegenerative disorder. Mutations in the NPC1 gene occur in 95% of patients, and the resultant NPC1 protein is misfolded and degraded or no longer capable of facilitating intracellular trafficking of lipids and cholesterol through the lysosome. There is currently no FDA-approved therapy for NPC, and thus there is a critical need to develop effective therapeutics to meet the needs of NPC patients. The long-term goal of this research is to address this need through the development of small-molecule autophagy modulators that restore lipid homeostasis in vivo. The overall objective of this proposal is to identify and optimize small molecules that modulate autophagy, improve the NPC phenotype in vitro, and restore lipid homeostasis in vivo while also extending life span. The rationale for this research is that various mechanisms of autophagy modulation, including early-stage inhibition, late-stage inhibition, and activation, have been reported to have potential therapeutic benefit in models of NPC. The central hypothesis of this research is that small molecules that modulate autophagy will alleviate cholesterol accumulation and extend life span of NPC mice. However, it is still unclear what mechanism of autophagy modulation is most beneficial, and this question will be a central focus of this research through unbiased identification of autophagy modulators that improve the NPC phenotype. This approach is innovative because it departs from the status quo of developing autophagy modulators and then exploring their effects in NPC and instead uses phenotypic screens to identify modulators that have a positive impact on NPC phenotypes with subsequent determination of the mechanism of autophagy modulation. Mass spectrometry imaging will be used as a novel method to determine modulator mechanism and to evaluate efficacy of autophagy modulators in vivo through the analysis of protein and lipid changes, which will also aid in the identification of biomarkers. The proposed research is significant because it will identify which mechanism of autophagy modulation is most beneficial in NPC, it will provide novel, small-molecule autophagy modulators with efficacy in NPC, and it will provide new strategies for the assessment of small-molecule mechanism in vivo without labeled probes. These advances will greatly contribute to the long-term goal of bringing new therapeutic options to NPC patients.


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: 2024 ( Subtotal = $385,586 )
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	3/11/2024	NON-COMPETING CONTINUATION	$347,028
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	3/18/2024	NON-COMPETING CONTINUATION	$0
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	5	4/26/2024	NON-COMPETING CONTINUATION	$38,558
2024	2023	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/28/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $385,586

Issue Date FY: 2023 ( Subtotal = $385,586 )
2023	2023	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/7/2023	NON-COMPETING CONTINUATION	$385,586
														Subtotal = $385,586

Issue Date FY: 2022 ( Subtotal = $385,586 )
2022	2022	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	3/30/2022	NON-COMPETING CONTINUATION	$385,586
														Subtotal = $385,586

Issue Date FY: 2021 ( Subtotal = $426,826 )
2021	2021	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	3/15/2021	SUPPLEMENT FOR EXPANSION	$41,240
2021	2021	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/13/2021	NON-COMPETING CONTINUATION	$385,586
														Subtotal = $426,826

Issue Date FY: 2020 ( Subtotal = $385,586 )
2020	2020	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/23/2020	NEW	$385,586
														Subtotal = $385,586

Grand Total All Awards = $1,969,170

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Development of autophagy modulators for evaluation as a therapeutic strategy for Niemann-Pick Type C

Award Number: R01NS114413

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer