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Developing an in vitro model for cancer pain using all-optical electrophysiology

Award Number: R43CA224563
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/22/2018
PERIOD OF PERFORMANCE END DATE: 12/31/2019

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Developing an in vitro model for cancer pain using all-optical electrophysiology - Project Summary Cancer pain therapeutics comprise more than one quarter of the total pain market. The current treatment paradigm relies on opioids, which are not effective for many patients and can have debilitating side effects for others. Despite the clear societal need for better pain medicines, there has been glacial progress in bringing new drugs to market. This shortfall is due in part to the lack of translatable model systems and tools to rapidly study relevant electrical and synaptic phenotypes associated with pain. We aim to overcome these challenges. The all-optical electrophysiology platform Optopatch, recently developed at Q-State Biosciences and comprised of engineered optogenetic proteins, custom microscopes, and software, makes it possible to simultaneously stimulate (blue light) and record (red light) electrical activity from around one hundred neurons with one millisecond temporal resolution, single cell spatial resolution and high signal-to-noise. The Optopatch platform can be used to study single-cell excitability, synaptic transmission, and network behavior with information content comparable to manual patch clamp, but at dramatically higher throughput. In this application, we propose to create an in vitro model of cancer pain via chemotherapeutics or mimicking the local tumor chemical environment experienced by sensory neurons. We will establish an Optopatch synaptic assay between primary rodent DRG neurons and dorsal horn neurons that will serve as the basis for phenotypic evaluation. Using our Optopatch excitability and synaptic assays, we will develop a “cancer pain soup” that consists of the relevant signaling molecules. This formulation will be validated in vitro using human stem cell-derived sensory neurons as well as in vivo with nociception assays in rodents. We hypothesize that addition of this chemical mixture will lead to a phenotype of hyperexcitability or increased synaptic transmission. We will screen established tool compounds and attempt to reverse the phenotype. The Phase I application will establish the cancer pain in vitro response that can be used for phenotypic drug screening efforts in Phase II to identify novel therapeutics for cancer pain.


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: 2020 ( Subtotal = $0 )
2020	2019	Q-STATE BIOSCIENCES, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	000	2	5/2/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $92,923 )
2019	2019	Q-STATE BIOSCIENCES, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	000	2	4/24/2019	NON-COMPETING CONTINUATION	$92,923
														Subtotal = $92,923

Issue Date FY: 2018 ( Subtotal = $207,076 )
2018	2018	Q-STATE BIOSCIENCES, INC.	179 SIDNEY ST	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Treatment Research	000	1	5/21/2018	NEW	$207,076
														Subtotal = $207,076

Grand Total All Awards = $299,999

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Developing an in vitro model for cancer pain using all-optical electrophysiology

Award Number: R43CA224563

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/22/2018

PERIOD OF PERFORMANCE END DATE: 12/31/2019

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