Epigenetic markers and sustained cytoprotection for stroke treatment
Active Project Grant Awarded Last action
- Award ID
- R42NS098918
- Recipient
-
Zymo Research Corporation UEI MNUYHHMKG8N9
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $7,451,161
Award facts
- Assistance listing
- 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
- Completion date 92% complete
- Originally
- Funding
-
- $6,368,447.00 Federal
- $1,082,714.00 Non-federal
- Place of performance
- Irvine, CA 92614, USA
Award details come from USAspending.gov.
Description
- Abstract
- Stroke injury occurs over a long duration through pathologic changes leading to long-term neurologic dysfunction. There is an urgent need of therapeutic strategies that can provide safe and efficacious therapeutic effects to the hypoperfused brain with long-lasting endogenous neuroprotection for prevention of long-term neurologic dysfunction. Sufficient evidence has pointed out 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. Researchers at the university of texas health science center at houston (utsch-h) have been able to incorporate XE into liposomes and demonstrated that XE-liposomal treatment post-stroke resulted in activation of endogenous brain protection following ischemic stroke. Corroborated mechanisms of XE cytoprotection include the activation of endogenous cytoprotective molecules. In a NIH phase i sttr, uthsc-h collaborated with zymo research corporation (zymo), an experienced epigenetics company. We have shown proof of concept that intermittent xenon(XE)-liposomal treatment after stroke extends endogenous neuroprotection and induces epigenetic changes. Such sustained endogenous neuroprotection can be distinguished by a panel of differentially methylated biomarkers indicative of activation of specific signal transduction pathways. As brain pathological changes/progression post stroke last for months, to be clinically useful, to extend the window for neuroprotection duration. We hypothesize that endogenous neuroprotection seen via epigenetic markers can be enhanced and consolidated and into the chronic recovery phase, meanwhile, translate to clinical relevant model. We do this with a three-phase xenon administration strategy. Two XE formulations, XE- liposomes and oral XE formulation, will be used to extend the treatment window. We will establish maximal therapeutic efficacy and then translate into aged RAT to increase rigor. The epigenetic biomarker panel identified in the phase i sttr will be used to assess and validate XE long term neuroprotective effects via the 3-phased administration regime in our phase 2 sttr. Our goal is to optimize, validate, and translate the XE liposomal formulation from phase i and evaluate a new complementary xenon cyclodextrin (XE-CD) formulation for oral administration for the chronic stroke recovery phase, whilst commercializing both XE intravenous and oral formulations. We will continue epigenetic biomarker development as a diagnostic tool for evaluating stroke progression and treatment effects. Our aims are: 1) to develop final formulations of XE-liposomes and XE-enriched solution, and to evaluate parameters for product reproducibility and analysis pharmacokinetics of both formulations; 2) to maintain neuroprotection over a longer duration by adding an oral XE-CD formulation following the IV acute XE-liposomal agent administration (acute to chronic recovery strokes) in both adult and aged animals; and 3) to finalize, and scale the XE-liposomal and XE-CD-oral formulations for an IND application. Our long-term goal is to bring this strategy and these two formulations into clinical trials to stabilize and treat stroke from the acute to the long term recovery phase.
Transactions
| Action | Federal | Non-federal | Date |
|---|---|---|---|
| Amendment | $907,735 | $0 | |
| Amendment | $980,725 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $631,721 | $0 | |
| Amendment | $841,419 | $0 | |
| Amendment | $841,419 | $0 | |
| Amendment | $1,082,714 | $0 | |
| Original award | $1,082,714 | $1,082,714 |
Show all 12
Quick answers
Who received award R42NS098918?
R42NS098918 was awarded to Zymo Research Corporation by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on May 1, 2017.
How much is award R42NS098918 worth?
$7,451,161 has been obligated on R42NS098918: $6,368,447 in federal funding and $1,082,714 in non-federal funding.
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