NEW YORK – Molecular diagnostic testing for stroke is in its infancy, but Ischemia Care hopes to change that by offering RNA-expression testing from a CLIA-certified laboratory in Ohio.
The company further expects its first molecular test for stroke will be available with US Food and Drug Administration clearance before the end of this year, and it has begun collaborating with IVD industry manufacturers to develop such tests for adoption in hospital laboratories, the firm's CEO Jeff June said in an interview.
Since 2014, Oxford, Ohio-based Ischemia Care and clinical investigators from 20 health systems have been using a combination of NGS, microarrays, and machine learning to identify RNA-expression patterns for stroke as part of a multicenter clinical trial called BASE, for Biomarkers of Acute Stroke Etiology.
Ischemia Care is using the findings from the clinical study to develop tests based on the gene expression patterns it discovered, aiming to provide insights into the diagnosis of stroke that until now have been unavailable to clinicians, June said.
The firm has an overall objective to drive use of such blood-based diagnosis to reduce disparities in stroke care and lower its costs through more accurate and more broadly available diagnostic testing, June added.
"Our blood testing identifies when stroke occurs as well as its underlying cause, and we believe that its availability will go a long way to reducing costs and improving outcomes for patients," he said.
In the BASE clinical trial, clinical investigators used Ischemia Care's whole-blood ICDx test to develop gene expression-based signatures, aiming to differentiate cardioembolic stroke from stroke caused by large-artery atherosclerosis.
The test detected cardioembolic stroke with 90 percent sensitivity and 70 percent specificity, and stroke from large artery atherosclerosis at 70 percent sensitivity and 90 percent specificity, June said, adding that the firm presented early results of the study at the American Heart Association International Stroke Conference last November.
Overall, the BASE trial investigators accumulated more than 5,000 patient blood samples from about 1,700 patients.
The samples were tested in Ischemia Care's laboratory to detect gene-expression patterns in patients who had presented with stroke symptoms and were determined by clinicians to have a range of stroke-related traits. Some were found to have a condition that imitated a stroke, a so-called stroke mimic. Others were found to have a stroke, and clinicians determined the underlying causes. Ischemia Care then conducted microarray testing on the blood samples to identify genetic signatures specific to the stroke subtypes.
The investigators identified gene-expression signatures associated with the detection of stroke, the detection of mimics, the timing of stroke, the detection of stroke caused by atrial fibrillation, and the differentiation of cardioembolism from large artery atherosclerosis as a cause of stroke, June said.
Based on results of this study, Ischemia Care has launched a laboratory-developed test to differentiate cardioembolism from large artery atherosclerosis as a cause of stroke, using a 45-gene signature, and it intends to seek FDA clearance before the end of this year using data from the BASE trial and follow-on studies.
In the future, the firm intends to also seek clearance for tests that determine whether stroke occurred or not; whether the patient suffered a transient ischemic attack or transient neurological event; and whether the cause of stroke was atrial fibrillation or another unknown cause. The firm is further developing gene expression tests as indicators of the risk for mortality and detection of comorbidities associated with stroke, June said.
Clinicians are getting better at diagnosing stroke, but current tests all have limitations, including the ability to provide the level of clinical detail needed, said Frank Peacock, an emergency department physician at Baylor College of Medicine and lead investigator on the BASE clinical trial.
Physicians use numerous methods to try to diagnose stroke, including reviewing a patient's medical history and symptoms, and try to determine when a stroke occurred as well as its cause. Each piece of information is crucial to how a stroke patient is treated, he said.
Physicians conduct CT scans partly "because there are so many mimics that look like strokes, and you have to sort that out," Peacock said. "If it looks like the patient has had a stroke based on a CT scan, it's highly likely that a clinician will treat the patient for stroke, but strokes occur frequently that don't show up on a scan." Some patients are also given MRI scans, which are expensive and not widely available, Peacock noted.
As a result, a blood test that provides information about whether a stroke has occurred and why it occurred "will be extremely useful," and help clinicians make important decisions about how to treat patients, Peacock said. Overall, Ischemia Care's "unique approach, which uses RNA expression for stroke testing, offers a tremendous amount of promise," he said.
If it obtains FDA clearance, the company intends to continue running its tests as a service from its laboratory, but it will also manufacture and sell kits for use by hospital laboratories.
"We work with each hospital to meet its specific use case," June said. "For example, a rural hospital system may be different from a large academic center," and some hospitals may not have the infrastructure to run testing on-site, he noted.
Ischemia Care currently uses microarray platforms as a basis of its laboratory-developed tests, but it is also developing assays to run on NGS and qPCR multiplex systems. June said it is working with IVD companies to optimize its assays to run on multiple platforms.
The company said that among a growing list of collaborators, it is partnering with Waltham, Massachusetts-based Thermo Fisher Scientific; Dayton, Ohio-based Kettering Medical Center; and Gainesville-based University of Florida Shands Hospital.