Project Details
Projekt Print View

Acid Sphingomyelinase Inhibition protects against experimental Multiple Sclerosis: mechanisms and translation to therapy

Subject Area Anatomy and Physiology
Term from 2007 to 2015
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 39134126
 
Multiple Sclerosis (MS) is a chronic demyelinating neuroinflammatory disease, mainly affecting young adults. Immigration of leukocytes into the central nervous system (CNS) is a main pathophysiological step in this disease and is based on mutual recognition of adhesion molecules. Our data show that mice deficient for acid sphingomyelinase (Asm) are completely resistant against development of experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. These findings could be reproduced by a functional blockade of Asm by the known anti-depressant amitriptyline. Asm deficiency protected against typical intraparenchymal inflammatory infiltrates. As possible mechanism, we deteced a significantly reduced adhesion of T cells to brain endothelial cells of Asm deficient or amitriptyline-treated T cells upon induction of EAE. These results may explain the observed protection of Asm blockade against EAE. In the present proposal, we further dissect (I) the cellular target of ASM in EAE (T versus endothelial cells), (II) the role of the Asm in leukocyte-endothelial interactions, (III) the specificity of our results for EAE by comparison with an other neurological autoimmune disease model and (IV) the translation to clinic by a pilot clinical trial on the effects of ASM inhibition in MS patients.
DFG Programme Priority Programmes
Participating Person Dr. Silke Walter
 
 

Additional Information

Textvergrößerung und Kontrastanpassung