Ischemia Care

Summary of the Technology

IIschemia Care’s technology is a blood test to help stratify ischemic stroke and TIA patients by cause – atheroembolic vs. cardioembolic - using leucocyte RNA isolated from whole blood.  The test is based on the observation that RNA expression differs and is unique in leucocytes depending on the nature and origin of the embolus causing the stroke.  

History

The platform technology is based on 14+ years of multicenter clinical research, encompassing over 1,000 patient samples across multiple stroke subtypes, led by Dr. Sharp and Dr. Jickling at the University of California – Davis. The research has attracted over  $5M in research funding from sources including the National Institutes of Health, National Institute of Neurological Disorders and Stroke, American Heart Association, and the Bugher Foundation.
This groundbreaking multicenter research was the first to identify in humans that RNA expression across numerous time points occurred in patterns that correlated with whether patients had an ischemic stroke from a cardioembolism (blood clot originating in the heart) or from atherosclerotic emboli (usually from a carotid artery) .  These observations initially made between 2000-2006 have been successfully validated in larger populations [ , ] between 2008-2012.  Additional IP and gene expression signatures have also been developed for hemorrhagic transformation, TIAs and lacunar strokes [ , , ].  
This early research and funding significantly reduced technical risk and provided “proof of concept data” prior to the licensing of the technology by ISC. Also, under a “Material Transfer Agreement” ISC obtained possession of the original RNA samples and data (array output files), that was then used for a retrospective validation study in the ISC laboratory.

References


Xu H, et al: Gene expression in peripheral blood differs after cardioembolic compared with large-vessel atherosclerotic stroke. J Cereb Blood Flow Metab 2008, 28(7):1320-1328.

Jickling GC, et al: Signatures of cardioembolic and large-vessel ischemic stroke. Ann Neurol. 2010 Nov;68(5):681-92.

Stamova B, et al:  Gene expression profiling of blood for the prediction of ischemic stroke. Stroke. 2010 Oct;41(10):2171-7. Epub 2010 Aug 26.

Jickling, G. C., et al: Profiles of lacunar and nonlacunar stroke. May 25, 2011 Ann Neurol., 70: 477–485. doi: 10.1002/ana.22497 

Tan, et al; Transient ischemic attacks characterized by RNA profiles in blood; Neurology November 8, 2011 77:1718-1724

Glen C. Jickling, MD; et al; Ischemic Transient Neurological Events Identified by Immune Response to Cerebral Ischemia; February 2. 2012

Studies completed to date

  • In 2001, researchers demonstrated that RNA expression profiles in peripheral blood were different 24 hours following ischemic stroke, ICH (intracranial hemorrhage), status epilepticus, hypoglycemia and hypoxia .
  • In 2006, researchers extended these studies, showing different RNA expression profiles in blood of patients with ischemic stroke .
  • In 2008 , using serial blood samples (3, 5, 24 hours) collected through a major clinical trial (CLEAR) from patients with acute ischemic stroke, researchers identified genes that correlate with whether patients had a stroke from the heart (cardioembolism) or a stroke from atherosclerosis emboli from the carotid artery.
  • In 2010, the previous studies were reproduced in two major peer reviewed publications [ , ] in larger populations. The technology was further applied to (1) cryptogenic outcomes for predicting cardioembolic cause of stroke, (2) identifying 37 probes differentiating atrial fibrillation from non-atrial fibrillation patients and (3) 97 probes differentiating stroke from mimics.
  • In 2011 and 2012, researchers developed additional findings on transient neurological events (TNEs), TIAs and lacunar strokes [ , , ].
  • In 2013, early research was performed related to hemorrhagic transformation.

 

References

Tang Y, et al: Blood genomic responses differ after stroke, seizures, hypoglycemia, and hypoxia: blood genomic fingerprints of disease. Ann Neurol 2001, 50(6):699-707.

Tang Y, et al: Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study. J Cereb Blood Flow Metab 2006, 26(8):1089-1102 Epub 2006 Jan 1084

Xu H, et al: Gene expression in peripheral blood differs after cardioembolic compared with large-vessel atherosclerotic stroke: biomarkers for the etiology of ischemic stroke. J Cereb Blood Flow Metab 2008, 28(7):1320-1328.

Jickling GC, et al: Signatures of cardioembolic and large-vessel ischemic stroke. Ann Neurol. 2010 Nov;68(5):681-92.

Stamova B, et al:  Gene expression profiling of blood for the prediction of ischemic stroke. Stroke. 2010 Oct;41(10):2171-7.

Jickling, G. C., et al: Profiles of lacunar and nonlacunar stroke. May 25, 2011 Ann Neurol., 70: 477–485. doi: 10.1002/ana.22497

Zhan, X., et al; Transient ischemic attacks characterized by RNA profiles in blood; Neurology November 8, 2011 77:1718-1724

Glen C. Jickling, MD; et al; Ischemic Transient Neurological Events Identified by Immune Response to Cerebral Ischemia; Feb 2. 2012