Tuesday, July 1, 2025 7/1/2025

Computational Drug Repurposing for AD/ADRD with Integrative Analysis of Real World Data and Biomedical Knowledge

Award Number: R01AG076234
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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Computational Drug Repurposing for AD/ADRD with Integrative Analysis of Real World Data and Biomedical Knowledge - ABSTRACT Alzheimer’s disease (AD) and AD-related dementia (AD/ADRD) is the 6th leading cause of death in the United States (US) – is an aging-related neurodegenerative disease with complex pathogenic mechanism affecting an estimated 6.2 million Americans in 2021. Both the pathogenic mechanism and pathophysiology of AD/ADRD are complex, creating difficulties in finding effective new treatment or prevention strategies, despite significant investments in the last decade. On the other hand, the proliferation of large clinical research networks (CRNs) with real-world data (RWD), such as electronic health records (EHRs), claims, and billing data among others, offer unique opportunities to generate real-world evidence (RWE) that will have direct translational impacts on AD/ADRD. In the past, RWD such as EHRs have limited use for AD/ADRD drug repurposing and primarily used only for validating and evaluating the hypotheses generated by molecular level predictions of AD/ADRD repurposing agents, partially due to a number of key methodological gaps: (1) the lack of integration with existing rich biological and pathophysiological knowledge of AD/ADRD for hypothesis generation, (2) the lack of validated computable phenotyping (CP) and natural language processing (NLP) algorithms and tools that can accurately define the study populations, extract key relevant patient characteristics and meaningful outcomes (e.g., MMSE scores to determine severity), (3) the lack of consideration on the heterogeneity of the disease (i.e., AD/ADRD subtypes), and (4) the lack of recognition of the inherent biases in RWD and the need of applying causal inference principles. The goal of this project is to develop a comprehensive machine learning based causal inference framework for generating high-throughput and high-quality drug repurposing hypotheses for AD/ADRD by integrating heterogeneous information sources. There are three aims in this project. Aim 1 aims at developing computable phenotypes to extract key patient characteristics and outcomes relevant to AD/ADRD drug repurposing studies from RWD. Aim 2 aims at developing a learning-based causal inference framework for generating drug repurposing hypotheses from RWD, a deep knowledge embedding framework for generating drug repurposing hypotheses from biomedical knowledge bases (BKB); and a mutual information enhancement framework that combines the information from both RWD and BKB to further improve the quality of the generated hypotheses. Aim 3 aims at validating the generated hypotheses with diverse data sources and approaches. The project will leverage the patient data from two large clinical research networks (CRNs) contributing to the national Patient-Centered Clinical Research Network (PCORnet) – covering ~15 million Floridians and ~11 million New Yorkers. The developed algorithms and software will be open sourced and widely disseminated within the CRNs and the AD/ADRD research communities.


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: 2025 ( Subtotal = $740,268 )
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Aging Research	000	4	3/10/2025	NON-COMPETING CONTINUATION	$679,837
2025	2025	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Aging Research	001	4	6/17/2025	NON-COMPETING CONTINUATION	$60,431
														Subtotal = $740,268

Issue Date FY: 2024 ( Subtotal = $766,946 )
2024	2024	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Aging Research	000	3	4/15/2024	NON-COMPETING CONTINUATION	$766,946
														Subtotal = $766,946

Issue Date FY: 2023 ( Subtotal = $775,212 )
2023	2023	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	2	3/23/2023	NON-COMPETING CONTINUATION	$775,212
														Subtotal = $775,212

Issue Date FY: 2022 ( Subtotal = $807,473 )
2022	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Aging Research	000	1	2/18/2022	NEW	$807,473
														Subtotal = $807,473

Grand Total All Awards = $3,089,899

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Computational Drug Repurposing for AD/ADRD with Integrative Analysis of Real World Data and Biomedical Knowledge

Award Number: R01AG076234

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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