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Epigenetic Markers and Sustained Cytoprotection for Stroke Treatment

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41NS098918-01A1
Agency Tracking Number: R41NS098918
Amount: $225,000.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 101
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-05-01
Award End Date (Contract End Date): 2019-04-30
Small Business Information
17062 MURPHY AVE
Irvine, CA 92614-5914
United States
DUNS: 927045336
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 KEITH BOOHER
 (949) 679-1190
 kbooher@zymoresearch.com
Business Contact
 JONATHAN CLAYPOOL
Phone: (949) 679-1190
Email: jclaypool@zymoresearch.com
Research Institution
 UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
 
7000 FANNIN STREET, UCT 1000
HOUSTON, TX 77030-5400
United States

 Nonprofit College or University
Abstract

PROJECT SUMMARY ABSTRACT
Stroke injury is a process that occurs over a long duration with pathologic changes that result in long term
neurologic dysfunction For stroke there exists an important need for a strategy that can provide safe and
efficacious stabilization to the hypoperfused brain and initialize long lasting endogenous neuroprotection for
prevention of long term neurologic dysfunction Sufficient evidence has shown that xenon Xe a bioactive gas
has profound neuroprotective effects with advantages of rapid diffusion across the blood brain barrier BBB with
minimal side effects In recent novel studies researchers at The University of Texas Health Science Center at
Houston UTHealth incorporated Xe into liposomes and demonstrated that Xe liposome treatment post stroke
resulted in activation of endogenous brain protection following ischemic stroke and subarachnoid hemorrhage
Corroborated mechanisms of Xe cytoprotection include the activation of endogenous cytoprotective molecules
Repetitive administration of Xe liposomes extends the protective effects over time Although the detailed
mechanisms underlying repetitive administration induced long term protection remain unclear emerging
evidence supports that such adaptive phenotypes are epigenetically mediated As epigenetic post conditioning
is highly related to the potency frequency and duration of stimuli we hypothesize that repetitive intermittent Xe
liposomal administration at an optimal frequency and duration can induce epigenetic post conditioning resulting
in long term effects This hypothesis leads to the collaboration between Zymo Research Corporation Zymo an
experienced epigenetics company and UTHealth UTHealth holds the patents containing the claims for the use
of Xe containing liposomes for prevention and treatment of stroke From a commercialization standpoint Xe
liposome is an attractive therapeutic candidate due to its low side effects and markedly high BBB diffusion The
goals of this proposal are to optimize the Xe liposomal administration protocol for long term cytoprotection and
to find the best epigenetic markers that directly correlate Xe treatment to long term cytoprotective effects in
stroke treatment
Our aims are to determine the optimal frequency and duration of Xe liposomal administration and
demonstrate sustained cytoprotection by repetitive Xe liposomal administrations for ischemic stroke treatment
and to determine epigenetic signatures to indicate Xe sustained cytoprotection
Our long term goals STTR Phase II and beyond are to develop an optimal Xe liposomal delivery strategy using
essential epigenetic markers to demonstrate acute and long term neuroprotection following stroke and to
translate this technology into a clinical product with sustained stroke stabilization effects PROJECT NARRATIVE
Stroke injury occurs over a long duration through pathologic changes leading to long term neurologic dysfunction
Neuroprotection targeted to the long term effect could prevent or slow neurovascular deterioration in progressive
ischemic stroke We aim to establish a novel therapeutic delivery strategy to stimulate long term endogenous
cytoprotection and tolerance to provide valuable opportunities for stroke treatment Identification of reliable
biomarkers to guide determination of best frequency and duration of xenon containing liposome delivery will
provide an efficacious and translatable therapeutic administration protocol that allows consistent long lasting
protection in diverse types of patients

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

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