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High-throughput profiling of compound abuse liabilities and identification of addiction-related drug targets using an iPSC-enabled platform

Award Number: R44DA048686
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2021

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High-throughput profiling of compound abuse liabilities and identification of addiction-related drug targets using an iPSC-enabled platform - Project Summary/Abstract The scale of the US opioid addiction crisis clearly evidences the critical need for breakthroughs to assess compound abuse liabilities and to enable discovery of new analgesics with minimal abuse potential. We hypothesize that altered addiction-associated physiology can be modeled in co-cultured hiPSC-derived neuronal and astrocyte cells and detected by profiling gene expression alterations and associated phenotypic readouts. Our proposal addresses the significant lack of physiologically-relevant tools capable of profiling relevant molecular changes that underpin addiction in the human nervous system by executing Specific Aims that encompass: (1) generation of a panel of multicolor hiPSC-derived neuronal and astrocyte cells with stable lineage specific fluorescent reporters; (2) execution of a phenotype-based pilot machine learning-enabled predictive abuse liability screen; and (3) combination of phenotypic profiling and gene expression analysis to characterize the molecular and cellular changes associated with compound exposure. Successful completion of our project will deliver 2 significant advances: (1) an important new technical framework to assess abuse potential of candidate therapeutics early in the development process and (2) an innovative, scalable in vitro assay platform that enables discovery of targets and associated candidate therapeutics to mitigate addiction phenotypes. These innovations will position Cairn Biosciences to initiate drug discovery programs that will bring significant societal benefit by helping to stem the growth of the US opioid crisis and reduce the mortality rates and economic burden associated with this National Emergency.


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: 2022 ( Subtotal = $0 )
2022	2019	CAIRN BIOSCIENCES, INC.	455 MISSION BAY BLVD SOUTH, SUITE 145	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Drug Use and Addiction Research Programs	000	1	10/22/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	CAIRN BIOSCIENCES, INC.	455 MISSION BAY BLVD SOUTH, SUITE 145	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Drug Use and Addiction Research Programs	000	1	4/30/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $323,750 )
2019	2019	CAIRN BIOSCIENCES, INC.	455 MISSION BAY BLVD SOUTH, SUITE 145	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Drug Use and Addiction Research Programs	000	1	9/13/2019	NEW	$323,750
														Subtotal = $323,750

Grand Total All Awards = $323,750

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High-throughput profiling of compound abuse liabilities and identification of addiction-related drug targets using an iPSC-enabled platform

Award Number: R44DA048686

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/30/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2021

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