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An all-optical electrophysiology platform for the discovery of pain therapeutics

Award Number: R44NS107041
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: 07/01/2018
PERIOD OF PERFORMANCE END DATE: 10/31/2021

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An all-optical electrophysiology platform for the discovery of pain therapeutics - Project Summary Chronic pain affects over 100 million adults in the United States and is challenging to treat. Current treatments include opioids and non-steroidal inflammatory agents. However, efficacy of these drugs in chronic treatment is restricted by dose limiting toxicities, and prolonged opioid use can lead to dependency. Despite the clear, unmet medical need and significant research activity, few drugs targeting pain based on novel, non-opioid mechanisms have appeared in the past decade. Q-state has created a novel all-optical platform (Optopatch) using engineered optogenetic proteins and custom microscopes to simultaneously stimulate and record electrical activity from a variety of cell types with high sensitivity and temporal resolution. We focus our efforts on a genetically validated pain target, SCN9A (Nav1.7), a voltage-gated sodium channel that is required for pain signal transmission in sensory neurons. We will apply Optopatch technology in two formats. 1) An HTS screen of the Q-State chemical library using a heterologously expressed Nav1.7 channel assay that replicates physiological spiking activity. Counterscreens against other Nav1.x channels will be performed in the same assay format to determine compound selectivity. 2) Identified inhibitors will be evaluated in medium throughput screens that measure excitability in rodent sensory and human iPS sensory neurons that have been sensitized using inflammatory mediators. This integrated set of assays is designed to identify Nav1.7 inhibitors acting by diverse working mechanisms and prioritize compounds for further optimization using scalable in vitro models of sensory neuron function. This platform will be employed as an efficient means to select compounds for optimization using medicinal chemistry and pharmacokinetic, drug metabolism and in vivo efficacy data.


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	2020	Q-STATE BIOSCIENCES	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	3/21/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $1,000,946 )
2020	2020	Q-STATE BIOSCIENCES, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	8/28/2020	NON-COMPETING CONTINUATION	$1,000,946
2020	2018	Q-STATE BIOSCIENCES, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/25/2020	NEW	$0
														Subtotal = $1,000,946

Issue Date FY: 2019 ( Subtotal = $731,940 )
2019	2019	Q-STATE BIOSCIENCES, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	8/22/2019	EXTENSION WITH OR WITHOUT FUNDS	$731,940
														Subtotal = $731,940

Issue Date FY: 2018 ( Subtotal = $222,370 )
2018	2018	Q-STATE BIOSCIENCES, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/20/2018	NEW	$222,370
														Subtotal = $222,370

Grand Total All Awards = $1,955,256

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An all-optical electrophysiology platform for the discovery of pain therapeutics

Award Number: R44NS107041

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: 07/01/2018

PERIOD OF PERFORMANCE END DATE: 10/31/2021

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