Researchers at Gladstone Institutes in San Francisco have created a molecular sensor that can detect multiple sclerosis (MS) early. The method is so precise that MS can be tracked long before disease onset when a patient first presents with symptoms.
Short of performing an autopsy, the only way doctors can currently diagnose MS is by a process of elimination. Many diseases mimic MS, so getting a definitive diagnosis can sometimes take months or years. In the meantime, the patient loses any benefit he or she might gain from starting disease modifying therapy (DMT) early.
But a team of scientists, led by Katerina Akassoglou, Ph.D., a senior investigator at Gladstone and a professor of neurology at the University of California, San Francisco, has found a molecular marker of MS disease activity that may one day become a test used to diagnose MS with certainty.
Shedding Light on the Disease Process
When the protective blood-brain barrier (BBB), which separates the body's blood supply from the brain and spinal cord, is compromised, a protein called fibrinogen leaks into the brain. This causes a chain reaction where thrombin, another protein, converts fibrinogen into fibrin—a protein not normally present beyond the BBB.
The body recognizes that something is amiss when fibrin appears in the brain, and it sends immune system defenders to respond. Akassoglou's theory is that this process causes damage to the myelin coating of nerve cells that characterizes MS.
"We already knew that the buildup of fibrin appears early in the development of MS, both in animal models and in human patients, so we wondered whether thrombin activity could in turn serve as an early marker of disease," said Akassoglou in a press release. "In fact, we were able to detect thrombin activity even in our animal models—before they exhibited any of the disease's neurological signs."
Using an Activatable Cell-Penetrating Peptide (ACPP), which acts as a molecular tracker, researchers were able to deliver a fluorescent agent into the brain and detect thrombin, causing it to light up.
“Our study showed that thrombin activity occurs early in the disease and correlates with the severity of neurologic symptoms in mice,” said Akassoglou in an interview with Healthline. “We hope that tracking thrombin might be indicative of the onset of disease activity in MS.”
Although they have not yet tested this theory in humans, the results from the mouse study are promising. The hope is to adapt the ACPP for use in humans so that thrombin build-up can be seen on magnetic resonance imaging (MRI) scans.
What's the Next Step?
“Our future work will focus on developing a sensitive thrombin sensor for MRI imaging and testing its efficacy to detect and maybe predict the appearance of MS lesions,” explained Akassoglou. “Combined with our work on developing new methods to target fibrin actions in the central nervous system, we hope that we will be able to [define] a new pathway that can be exploited for early MS detection and the discovery of new treatments.”
This is great news for anyone who is in diagnosis “limbo.” With a single MRI scan, fluorescing thrombin could give patients the answer they need. While neurologists already use MRI as a diagnostic tool, the presence of thrombin would leave no doubt as to the cause of a patient's symptoms.
The research team isn’t stopping there, though. Akassoglou is interested in preventing the destructive fibrin build-up from forming in the first place. “My laboratory is currently working on developing specific inhibitors of fibrin actions in the central nervous system to halt the destruction caused to axons and myelin,” she said.