Early detection of MS possible with novel molecular sensor

Using a molecular sensor that finds the protein fibrinogen in the blood-brain barrier, researchers are able to detect early signs of multiple sclerosis (MS) before any outward symptoms of disease. This could lead to better therapies provided earlier in the disease process, according to a study published Nov. 29 in the Annals of Neurology.

Katerina Akassoglou, PhD, senior investigator at Gladstone Institutes and professor of neurology at the University of California, San Francisco, and colleagues used molecular fluorescence imaging in this preclinical study to track thrombin in the brains of mice. The theory behind the study is that compromised blood-brain barriers allow passage of fibrinogen into the brain, causing the protein thrombin to convert fibrinogen into fibrin, which is involved in blood clotting and not usually found beyond the blood brain barrier. The presence of fibrin in the brain kicks off an autoimmune response that could destroy nerve cell myelin, a key component of MS development.

"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 Gladstone Institutes media 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."

Researchers developed a fluorescent probe that uses activatable cell-penetrating peptide (ACPP) to target thrombin activity in the brain. Results showed that thrombin activity occurred before any onset of neurological symptoms and increased at the height of disease, which was also associated with the build up of fibrin, stripping of myelin, damage to axons and microglial activation.

“Mice with genetic deficit in prothrombin confirmed the specificity of the thrombin probe," wrote the authors. "Thrombin activity might be exploited for developing sensitive probes for preclinical detection and monitoring of neuroinflammation and MS progression.

The next step is to develop a molecular MRI thrombin sensor to screen for MS lesions and potentially to predict likely development of disease. Further research could lead to fibrin-inhibiting therapies to treat MS.