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Identifying activators of interferon regulatory factors for neuroprotection

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R42NS095538-02
Agency Tracking Number: R42NS095538
Amount: $1,261,227.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: 106
Solicitation Number: PA15-270
Timeline
Solicitation Year: 2015
Award Year: 2016
Award Start Date (Proposal Award Date): 2016-09-30
Award End Date (Contract End Date): 2019-08-31
Small Business Information
17367 CANAL CIR
Lake Oswego, OR 97035-5619
United States
DUNS: 079179165
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 MARY STENZELPOORE
 (503) 494-2423
 poorem@ohsu.edu
Business Contact
 FRANCES BAHJAT
Phone: (503) 860-2988
Email: renabahjat@me.com
Research Institution
 OREGON HEALTH & SCIENCE UNIVERSITY
 
3181 SW Sam Jackson Pk Rd
PORTLAND, OR 97239-3098
United States

 Nonprofit college or university
Abstract

Abstract
Stroke is a leading cause of morbidity and mortality in the United States However less than of patients
are eligible for the current approved interventions of tissue plasminogen activator or thrombectomy We seek to
develop new therapeutics to reduce the extent of damage and functional impairment resulting from ischemic
injury to the brain an area of significant unmet medical need We have found that interferon regulatory factor
IRF mediated gene transcription may represent an endogenous mechanism of neuroprotection that is
associated with a reduction in ischemic injury Using both cell and mouse models of stroke we have
demonstrated that administration of compounds following the ischemic insult that are known to induce IRF
mediated gene transcription significantly reduces the extent of damage These results indicate that activation
of IRF transcription factors following stroke may be a viable therapeutic intervention for the treatment of stroke
patients The ultimate goal of this STTR program is to identify compounds that induce IRF transcription in both
mouse and human cells but with minimal off target immune activity We will identify compounds with
acceptable target specification optimize these compounds through hit to lead protocols and ultimately test for
efficacy in a mouse model of cerebral ischemic injury
We propose the following aims
Aim Identify lead compounds for therapeutic development of an acute neuroprotectant using an
experimentally validated high throughput screening platform
Aim Evaluate and rank lead compounds through hit to lead characterization
Aim Evaluate PK and tolerability of lead compounds and determine efficacy in a mouse model of
cerebral ischemic injury Narrative
Stroke is a leading cause of morbidity and mortality in the United States with approximately cases a
year reported This proposal seeks to identify and validate small molecule activators of interferon regulatory
factors as potential mediators of neuroprotection with the ultimate goal being the development of a stroke
therapeutic

* Information listed above is at the time of submission. *

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