Endothelin-1 (ET-1) — a molecule with potent blood vessel-narrowing (vasoconstrictive) properties — may be used as a biomarker of severity for optic neuritis in people with multiple sclerosis (MS), a small Italian study suggests. The molecule also may be a potential indicator of patients’ failure to recover from this inflammation of the optic nerve.
The researchers said that detecting ET-1 levels may help to identify those individuals with MS who might benefit from anti-ET-1 therapies. One such therapy is Tracleer (bosentan), by Actelion Pharmaceuticals — approved for the treatment of pulmonary arterial hypertension — which is currently being evaluated as a potential treatment for MS in a Phase 2 trial in Belgium (2017-001253-13).
The study, “Increased Levels of Endothelin-1 in Cerebrospinal Fluid Are a Marker of Poor Visual Recovery after Optic Neuritis in Multiple Sclerosis Patients,” was published in the journal Disease Markers.
Cerebral blood flow is tightly regulated to meet the brain’s energetic demands. Cerebral hypoperfusion — decreased brain blood supply — has been reported in MS patients, and is directly associated with neurodegeneration, loss of myelin (the protective sheath around nerve fibers), and fatigue.
Researchers hypothesized that cerebral hypoperfusion in MS may be mediated by high levels of ET-1, released by reactive brain cells called astrocytes in MS lesions.
ET-1 induces vasoconstriction, or the tightening of blood vessels due to contraction of their muscular wall. Astrocytes are involved in the regulation of blood flow and inflammation, and respond to sites of nerve cell injury or chronic neurodegeneration by becoming “reactive.”
Optic neuritis results from inflammation and demyelination — loss of myelin — of the optic nerve, which transmits information from the eyes to the brain. Pain and temporary vision loss characterize the condition, and it is one of the most common first manifestations of MS.
According to the team, while most MS patients with optic neuritis recover completely within a few days or weeks, nearly 10% show incomplete recovery with permanent visual damage.
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