In a new study by Investigator Katerina Akassoglou, from Gladstone Institutes, scientists reveal in animal models that the heightened activity of a protein called thrombin in the brain could serve as an early indicator of MS.
By developing a fluorescently labelled probe specifically designed to track thrombin, the team found that active thrombin could be detected at the earliest phases of MS – and that this active thrombin correlates with disease severity.
These findings could spur the development of a much-needed early-detection method for this devastating disease, scientists said.
MS, which afflicts millions of people worldwide, develops when the body's immune system attacks the protective myelin sheath that surrounds nerve cells.
This attack damages the nerve cells, leading to a host of symptoms that include numbness, fatigue, difficulty walking, paralysis and loss of vision.
While some drugs can delay these symptoms, they do not treat the disease's underlying causes. In laboratory experiments on mice modified to mimic the signs of MS, the team employed an Activatable Cell-Penetrating Peptide (ACPP), a special type of molecular probe that delivers fluorescent agents to a region of interest.
For this study, they developed a thrombin-specific ACPP that could track thrombin activity in mice as the disease progressed. They then carefully analysed where—and at what stage of disease—thrombin activity was found.
"We detected heightened thrombin activity at specific disease 'hot-spots,' regions where neuronal damage developed over time," said Dimitrios Davalos, one of the paper's lead authors.
"And when we compared those results to those of a separate, healthy control group of mice, we saw that thrombin activity in the control group was wholly absent," said Davalos.
"Our results are proof of principle that a thrombin-specific molecular probe could be used as an early-detection method," added Kim Baeten, the paper's other lead author.
The study was published in the journal Annals of Neurology.


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