Medical Device Daily Associate

Researchers at the Cleveland Clinic (Cleveland) reported that they have received a U.S. patent for technology they developed to measure damage to a person’s blood-brain barrier, which is responsible for blocking foreign substances from reaching the brain.

The patent covers the researchers’ work to develop a blood test capable of indicating when the blood-brain barrier has been compromised, if neuronal damage exists, and when the person might be more responsive to medications that need to reach the brain to treat tumors or other neurological disorders.

The patent was issued to Cleveland Clinic researchers Damir Janigro, PhD, and Gene Barnett, MD. Janigro is a professor of molecular medicine and director of cerebrovascular research for the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University (also Cleveland). Barnett is director of the Cleveland Clinic Brain Tumor Institute.

“Determining the integrity of the blood-brain barrier is crucial in understanding disease states,” Janigro told Medical Device Daily. “Manipulating, predicting and preventing the opening or closing of the barrier helps physicians treat patients with many different medical problems. This blood test is a quick and easy way to determine the most appropriate treatment for many different patients.”

The blood test would provide a minimally invasive alternative to the painful spinal taps for cerebrospinal fluid currently taken to assess the condition of a patient’s blood-brain barrier. In addition, Janigro said, this blood test has the potential to save “hundreds of millions of dollars in MRI and CT scan costs,” since it could be used instead of the more costly diagnostic tests.

Barnett pointed to perhaps the most important application for such a test: “This test could prove useful in the early detection of brain tumors, particularly in patients with lung, breast or other systemic cancers where the risk of their cancer spreading to the brain is one in four.”

The work of Janigro and Barnett has shown that when a high level of S100b, a protein normally found in brain cells, is detected in the bloodstream, it can signal a disruption of the blood-brain barrier. This disruption, in turn, can indicate the presence of a brain tumor or brain injury. In contrast, when an individual’s blood-brain barrier is intact or working properly, the level of S100b in the bloodstream is low or even undetectable.

“Really what you’re measuring is the passage of protein from the blood to the brain,” said Janigro. He added that the test works in much the same way as the traditional spinal tap, albeit in a much less invasive fashion.

Janigro said the test already has a prior history. It originally was developed by Sangtec Molecular Diagnostics (Bromma, Sweden) as a blood marker for determining traumatic brain injury. But he said that the test had no value for that indication because there already are many ways to detect the condition, and such a test wouldn’t really present any value to patients if they already are presenting with such an injury.

However, he noted the brain injury test “with a barrier” has two advantages. “One, that it tells you that maybe brain injury will follow [and] gives you a window of opportunity to do something about it.” Secondly, he noted that such a test provides “a very inexpensive way to screen patients for MRI.”

The most widespread use of the marker for scientific purposes has been in cardiothoracic surgery, which was how the test originally made it to the Cleveland Clinic, Janigro said. “[Sangtec] exported this concept to a pediatric practice in cardiothoracic surgery at the clinic. That’s how I heard about it.”

The doctors at the clinic were using it to measure brain damage in patients whose hearts were not pumping enough oxygen to the brain, and Janigro discovered that what really was being measured was blood-brain barrier damage. “This is how we said ‘let’s explore this thing together and find a patent, because such a test does not exist.’”

As an example of the potential savings that can be achieved with such a test, he pointed to its potential use in lung cancer patients. The standard of care in a good hospital, he said, is currently to give a lung cancer patient an occasional MRI to see if the cancer has metastasized to the brain. “You scan everybody and spend $1,500 a pop . . . and yet we know that 90% of the patients are negative, if not more. What we discovered in our studies is that if you now pre-select these patients by doing an S100b test, you can pinpoint those [patients] who do not need a scan.”

While Janigro said that this test could save “on the order of hundred of millions of dollars per year nationwide,” that figure only included metastatic brain cancer scans and only in the U.S. and does not include all the other potential uses in such areas as battlefield trauma, sports medicine or use in an ambulance. Ultimately, he said the test could be used “in any condition for which contrast-enhanced MRI is recommended.”

The problem with some of the other potential uses, he said, is that one would need a point-of-care test to make them possible; currently the test must be performed in a hospital and requires a laboratory. “We are working on that aspect now,” he said.

CCF Innovations, the Cleveland Clinic’s technology transfer arm, is working to commercialize the technology through a license or a new company.

“Now we have the patent, but we don’t have any proprietary point-of-care test,” Janigro said. “We’re looking for partners who are interested in licensing this technology from us.”

Such a test, he said, would be “relatively simple” to produce since it would be a simple binary test, much like the one used to determine a pregnancy. A quantitative “big picture” test would be done only if the results were positive. “It just tells you yes, I need an MRI, or no, I don’t need an MRI.”