I was doing some research on Fingolimod when I stumbled onto something I thought may be related to the discussions we are having here. Fingolimod is a sphingosine 1-phosphate (S1-P) receptor modulator and has been shown to reduce relapses and disability progression. When I googled "sphingosine 1-phosphate (S1-P) receptor modulators," the research article below popped up. In it, the research shows that S1-P significantly attenuates "vascular barrier dysfunction." I have a limited understanding of CCSVI, but doesn't this fit in with the vascular angle of CCSVI? Any thoughts?
Mcverry, B.J., X. Peng, P.M. Hassoun, S. Sammani, B.A. Simon, and J.G.N. Garcia (2004). Sphingosine 1-phosphate reduces vascular leak in murine and canine models of acute lung injury. American Journal of Respiratory and Critical Care Medicine 170(9): 987-993. ISSN: 1073-449X.
NAL Call Number: RC705 .A4
Abstract: Excessive mechanical stress is a key component of ventilator-associated lung injury, resulting in profound vascular leak and an intense inflammatory response. To extend our in vitro observations concerning the barrier-protective effects of the lipid growth factor sphingosine 1-phosphate (Sph 1-P), we assessed the ability of Sph 1-P to prevent regional pulmonary edema accumulation in clinically relevant rodent and canine models of acute lung injury induced by combined intrabronchial endotoxin administration and high tidal volume mechanical ventilation. Intravenously delivered Sph 1-P significantly attenuated both alveolar and vascular barrier dysfunction while significantly reducing shunt formation associated with lung injury. Whole lung computed tomographic image analysis demonstrated the capability of Sph 1-P to abrogate significantly the accumulation of extravascular lung water evoked by 6-hour exposure to endotoxin. Axial density profiles and vertical density gradients localized the Sph 1-P response to transitional zones between aerated and consolidated lung regions. Together, these results indicate that Sph 1-P represents a novel therapeutic intervention for the prevention of pulmonary edema related to inflammatory injury and increased vascular permeability.
Descriptors: pharmacology, respiratory system, respiration, lung injury, injury, respiratory system disease, pulmonary edema, respiratory system disease, drug therapy, pathology, prevention and control, mechanical ventilation, clinical techniques, therapeutic and prophylactic techniques, tomography, diagnostic techniques, imaging and microscopy techniques, laboratory techniques, mechanical stress.