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A New Anti-inflammatory Therapy for Ischemic Stroke

Award Number: R41HL156322
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2020
PERIOD OF PERFORMANCE END DATE: 12/14/2022

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A New Anti-inflammatory Therapy for Ischemic Stroke - PROJECT SUMMARY Current therapy for ischemic stroke is limited and new treatment is needed since the mortality and morbidity of subjects with this condition remain high. Effort aimed at blocking immune cell- mediated inflammation represents a novel approach. The specific background for the proposed project is that we have identified the myeloid P2X4 receptor (P2X4R), which induces inflammation, as a new therapeutic target for ischemic stroke. Through our collaboration with Dr. Kenneth A. Jacobson, we have synthesized new small molecule antagonists at the P2X4R based on their prototypes and their efficacy in reducing stroke infarct size and improving functional behavioral outcomes. This structure-activity relationship study provided guidance on the type of compounds that may have anti-stroke efficacy. The goal here is to screen the new compounds for their affinity and selectivity at human P2X4R vs. other major human P2X receptors, and then perform preclinical proof of concept studies for efficacy in an established murine ischemic stroke model as well as in blocking P2X4R in myeloid cells of stroke patients. Cornovus is a company, in collaboration with its academic partner University of Connecticut School of Medicine’s research laboratories, and Laboratory of Bioorganic Chemistry of the National Institute of Diabetes, Digestive and Kidney Diseases of NIH, is well-positioned to perform the proposed feasibility studies. The objective of the grant is to screen and identify two lead compounds and then test them in the in vivo murine ischemic stroke model and the ex vivo human myeloid cell model obtained from ischemic stroke patients. The proposed studies should add to scientific knowledge on the chemistry and pharmacology of P2X4 antagonists and may also yield new insights into the science of such an anti-inflammatory approach. Pending successful outcomes, the proposal should position the company to pursue IND-enabling studies in the future.


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	CORNOVUS PHARMACEUTICALS INC.	400 FARMINGTON AVE	FARMINGTON	CT	06032	CAPITOL	USA	Cardiovascular Diseases Research	000	1	11/9/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $433,483 )
2021	2021	CORNOVUS PHARMACEUTICALS INC.	261 SAINT RONAN ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cardiovascular Diseases Research	000	1	12/11/2020	NEW	$433,483
														Subtotal = $433,483

Grand Total All Awards = $433,483

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A New Anti-inflammatory Therapy for Ischemic Stroke

Award Number: R41HL156322

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/15/2020

PERIOD OF PERFORMANCE END DATE: 12/14/2022

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