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New Approach to Atopic Dermatitis

Award Number: R43AR072546
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2018
PERIOD OF PERFORMANCE END DATE: 08/31/2021

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New Approach to Atopic Dermatitis - PROJECT SUMMARY: Current thinking has provided substantial support for the hypothesis that primary afferent and neuraxial neurogenic peptide receptors play a prominent role in pruritic pathologies. Of equal interest, is the growing appreciation that receptor signaling may also play a facilitatory role in inflammation in disease states. The confluence of these phenomena emphasize the likely importance of peripherally acting receptors in regulating aberrant sensations in pruritic states including atopic dermatitis (AD). Our data and literature support a link between neurogenic peptides to signaling by the Mas related GPCR family and that this signaling is governed by the transient receptor potential cation channel, member A1 (TRPA1). Accordingly, functional TRPA1 antagonists are expected to be key regulators of conditions like AD in terms of both pruritus and cutaneous inflammation. The goal of this application is to optimize one or more small molecule antagonists of the TRPA1 channel as a probe to study in vivo efficacy in animal models of AD. In this proposal, the drug discovery team at Epigen Biosciences Inc. will conduct a lead identification plan to identify novel small molecules with suitable drug like properties for pre-clinical evaluation of efficacy in preclinical models of atopic dermatitis. New compounds will be optimized for metabolic stability. Compounds with adequate in vitro profile will be studied at University of California San Diego (UCSD) in mice to identify compounds that prevent scratching responses. A lead compound will be further assessed in a preliminary model of atopic dermatitis for its ability to block behavioral responses and suppress preliminary markers of inflammation. Studies in atopic dermatitis will provide data on measures of dermal integrity [epidermal water loss and skin thickness], histopathology and measures of cytokine levels [protein and RNA from qPCR]. These data are expected to demonstrate the utility of novel TRPA1 antagonists in atopic dermatitis and support a lead optimization program as a prelude to commercial development. The lead compound will be then assessed for drug profile risk [cytochrome P450 and hERG inhibition] to guide future work.


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	2018	EPIGEN BIOSCIENCES INC.	10225 BARNES CANYON RD, STE A104	SAN DIEGO	CA	92121	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	2/17/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2018	EPIGEN BIOSCIENCES INC.	10225 BARNES CANYON RD, STE A104	SAN DIEGO	CA	92121	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	10/19/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $225,000 )
2018	2018	EPIGEN BIOSCIENCES INC.	10225 BARNES CANYON RD, STE A104	SAN DIEGO	CA	92121	SAN DIEGO	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	8/23/2018	NEW	$225,000
														Subtotal = $225,000

Grand Total All Awards = $225,000

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New Approach to Atopic Dermatitis

Award Number: R43AR072546

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2018

PERIOD OF PERFORMANCE END DATE: 08/31/2021

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