Inhibition of Vascular Endothelial Cell-Mediated Phagocytic Processes for Treatment of Demyelinating Conditions
The present invention concerns a method for treating a demyelinating condition by administering an agent that inhibits vascular endothelial cell phagocytosis. The method of the invention is useful in treating demyelinating conditions associated with an injury such as a spinal cord injury or traumatic brain injury as well as other demyelinating conditions such as multiple sclerosis.
The inventor has established a previously unidentified role for microvascular endothelial cells (EC) which have been shown to engulf and clear myelin debris in spinal cord injury and multiple sclerosis animal model systems. The inventor also discovered a novel pathway for myelin debris degradation through the autophagy-lysosome system. Importantly, the inventor demonstrated for the first time that microvascular EC uptake exerts critical functions beyond myelin debris clearance. Engulfment and autophagic processing of myelin debris by microvascular ECs have sequential consequences in promoting chronic inflammation and pathological healing (angiogenesis and fibrotic scar formation) during the progression of demyelinating disorders. Therefore, this research reveals how myelin debris engulfment and processing by microvascular ECs contribute to pathological progression in demyelinating disorders.