Scientists at Gladstone Institutes have developed a new molecular sensor that can detect multiple sclerosis before the onset of physical symptoms. Millions of people worldwide are diagnosed with multiple sclerosis—a disease that develops when the body’s immune system attacks the protective myelin sheath that surrounds nerve cells. This attack leads to a range of symptoms such as numbness, fatigue, loss of vision, difficulty walking and possible paralysis. Regardless of whether the disease attacks the individual progressively in spurts or instantaneously and without warning, the disease has always been present in the nervous system. Even the most sophisticated detection methods could not seem to penetrate to the root of the disease until the protein thrombin was analyzed and studied.
Dr. Akassoglou and her team knew that a key piece in progression of multiple sclerosis is the disruption of the blood brain barrier, which separates the brain from the blood circulating. When this barrier breaks down, a blood protein called fibrinogen leaks into the brain, which ultimately causes the protein thrombin to convert fibrinogen to fibrin—a protein that should not be present in the brain. As fibrin proteins accumulate this triggers an immune response that leads to the stripping away of the myelin sheath and contributes to the progression of multiple sclerosis.
Since the scientists knew that the buildup of fibrin occurred in both animals and human, they took to the lab to discover whether thrombin activity could serve as an early marker for this disease. In lab experiments with mice, the researchers created a fluorescent thrombin-specific Activatable Cell-Penetrating Peptide (ACPP) that would monitor thrombin activity in mice as the disease progressed. After carefully analyzing where and at what stage of the disease the thrombin activity was found in these mice, they compared those results to the results of healthy mice and discovered that there was no thrombin present within the healthy mice. These results give support to the idea that thrombin activity is directly correlated with the degradation of the nerve cell’s myelin sheath and can possibly serve as an early detection method for multiple sclerosis.
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