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A phenotypic screen for osteoarthritic pain therapeutics using all-optical electrophysiology.

Award Number: R44AR074820
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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A phenotypic screen for osteoarthritic pain therapeutics using all-optical electrophysiology. - Project Summary: A phenotypic screen for osteoarthritic pain therapeutics using all- optical electrophysiology Chronic pain affects over 100 million adults in the United States, many of whom cannot find relief with current medications. Of these patients, nearly 1/3 of them suffer from osteoarthritis. Current treatments for chronic pain include opioids and non-steroidal inflammatory agents. However, efficacy of these drugs in chronic treatment is restricted by the development of tolerance and dose-limiting toxicities. Opioids in particular are highly addictive, and dependency has caused a large societal burden. Despite the clear, unmet medical need and significant research activity, few new classes of non-opioid drugs targeting chronic pain have appeared in the past decade. Quell Therapeutics uses the Optopatch platform for making all-optical electrophysiology measurements in neurons at a throughput sufficient for phenotypic screening. Using engineered optogenetic proteins, blue and red light can be used to stimulate and record neuronal activity, respectively. Custom microscopes enable electrophysiology recordings from 100’s of individual neurons in parallel with high sensitivity and temporal resolution, a capability currently not available with any other platform screening technology. Here, we combine the Optopatch platform with an in vitro model of chronic pain, where dorsal root ganglion (DRG) sensory neurons are bathed in a mixture of inflammatory mediators found in the joints of osteoarthritis patients. The neurons treated with the inflammatory mixture become hyperexcitable, mimicking the anticipated cellular pain response. We calculate the functional phenotype of arthritis pain, which captures the difference in action potential shape and firing rate in response to diverse stimuli. We will screen for small molecule compounds that reverse the pain phenotype while minimizing perturbation of neuronal behavior orthogonal to the pain phenotype, the in vitro “side effects.” We will counter-screen against neurons from the cerebral cortex and cardiomyocytes from the heart to prioritize compounds that act selectively in inflamed sensory neurons. The highest ranking compounds will be chemically optimized and their pharmacokinetic, drug metabolism, and in vivo efficacy will be characterized. Our goal is to advance therapeutic discovery for pain, which may ultimately help relieve the US opioid crisis.


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 = $0 )
2024	2021	QUELLTX INC	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	7/15/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	QUELLTX INC	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	5/17/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	QUELLTX, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	3	8/18/2022	NON-COMPETING CONTINUATION	$0
2022	2019	QUELLTX, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	6/8/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $696,518 )
2021	2021	QUELLTX, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	9/6/2021	NON-COMPETING CONTINUATION	$696,518
														Subtotal = $696,518

Issue Date FY: 2020 ( Subtotal = $892,810 )
2020	2020	QUELLTX, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	002	2	9/16/2020	EXTENSION WITH OR WITHOUT FUNDS	$0
2020	2020	QUELLTX, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	001	2	8/24/2020	EXTENSION WITH OR WITHOUT FUNDS	$892,810
2020	2019	QUELLTX, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	12/3/2019	NEW	$0
														Subtotal = $892,810

Issue Date FY: 2019 ( Subtotal = $230,695 )
2019	2019	QUELLTX, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	9/20/2019	NEW	$230,695
														Subtotal = $230,695

Grand Total All Awards = $1,820,023

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A phenotypic screen for osteoarthritic pain therapeutics using all-optical electrophysiology.

Award Number: R44AR074820

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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