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Pharmacologic Suppression of Reperfusion Injury Following Endovascular Thrombectomy In Stroke.

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41NS110252-01A1
Agency Tracking Number: R41NS110252
Amount: $247,352.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 102
Solicitation Number: PA18-575
Solicitation Year: 2018
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-09-15
Award End Date (Contract End Date): 2021-08-31
Small Business Information
4650 S FOREST ST, Englewood, CO, 80113-6100
DUNS: 079124042
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (919) 684-6633
Business Contact
Phone: (303) 808-7314
Research Institution
 2200 W MAIN ST, SUITE 820
DURHAM, NC, 27705-4673
 Nonprofit college or university
Ischemic stroke is a leading cause of death and disability in the United StatesThis often is attributable to thrombus formation at an atherosclerotic plaque or thromboembolismPatients who present withinhours of symptom onset are eligible for thrombolysis with tissue plasminogen activatortPAThis serves andltof victimsRecentlymajor advance has been made with proven efficacy from endovascular mechanical thrombectomy in combination with tPADespite thisandltof treated patients have a good recoveryBasic and clinical science indicate that abrupt restoration of oxygen delivery to ischemic tissue causes reperfusion injury that amplifies propagates adverse cascades initiated by the initial ischemic insultThere has been widespread call for pharmacologic intervention to mitigate reperfusion injuryThe mechanistic basis for reperfusion injury is diversebut fundamentally associated with rapid onset dysfunction of intracellular mechanisms responsible for regulation of oxygen metabolismThis leads to oxidative stressinflammationapoptosisblood brain barrier disruption and tissue damageWe are working closely with chemists who have synthesized manganese porphyrinsMnPMnP have been highly characterized and serve as potent catalytic oxidoreductantsMnP have extraordinary efficacy to favorably modulate redox mediated activation of transcription factorse gNF kBNrfand MAPK and phosphatasesMnP also serve as potent catalytic reductants of reactive oxygen nitrogen speciesWe have repeatedly shown enduring improvement in experimental stroke long term outcome after therapeutic MnP dosingThe lead MnPBMXnow in human trials as a radioprotectant for normal tissue in the context of radiotherapy for brain malignancyhas achieved GMP synthesisscale up technologyand requisite preclinical toxicological screeningBased on highly encouraging pilot datawe propose BMXgiven at endovascular thrombectomy reperfusion onsetas an adjunct pharmaceutical to optimize endovascular thrombectomy outcomeIn Phasewe will define optimal dosing and maximal ischemia duration before reperfusion and treatment onset that retains efficacymeasure long term functional outcome in agedmetabolic syndromeand spontaneously hypertensive ratsdefine interactions with tPA activityand obtain independent laboratory efficacy validationA Clinical Trial Consulting Teamconsisting of independent stroke expertswill work in collaboration with Biomimetix to monitor go no go end points and develop protocols for human dose escalation trials PROJECT NARRATIVE Stroke treatment has been revolutionized by advance of endovascular thrombectomyyet andgtof stroke patients undergoing thrombectomy fail to recover independent status due to damaged brainThis Phase I STTR proposes execution of a series of preclinical efficacy assessments of BMXas an adjunct to endovascular thrombolysis to salvage injured brain and improve outcomeSuccessful completion of this Phase I STTR will provide the appropriate foundation for design and implementation of Phaseclinical trials of BMXin endovascular thrombectomy stroke patients

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

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