Epub: Hemmati et al. Neurorestorative effect of FTY720 in a rat model of Alzheimer’s disease: Comparison with Memantine. Behav Brain Res. 2013 Jun.
Alzheimer’s disease (AD) as a neurodegenerative brain disorder is the most common cause of dementia. To date, there is no causative treatment for AD and there are few preventive treatments either. The sphingosine-1-phosphate receptor modulator FTY720 (fingolimod) prevents lymphocytes from contributing to an autoimmune reaction and has been approved for multiple sclerosis treatment. In concert with other studies showing the anti-inflammatory and protective effect of FTY720 in some neurodegenerative disorders like ischemia, we have recently shown that FTY720 chronic administration prevents from impairment of spatial learning and memory in AD rats. Here FTY720 was examined on AD rats in comparison to the only clinically approved NMDA receptor antagonist, Memantine. Passive avoidance task showed significant memory restoration in AD animals received FTY720 comparable to Memantine. Upon gene profiling by QuantiGeneplex, this behavioral outcomes was concurrent with considerable alterations in some genes transcripts like that of Mitogen Activated Protein Kinases (MAPKs) and some inflammatory markers that may particularly account for the detected decline in hippocampal neural damage or memory impairment associated with AD. From a therapeutic standpoint, our findings conclude that FTY720 may suggest new opportunities for AD management probably based on several modulatory effects on genes involved in cell death or survival.
Whilst this may seem inherently uninteresting to MSers as this is about studies in animals related to Alzheimer’s disease, the interesting thing is that it appears to be influencing a degenerative condition which is not typically associated with autoimmunity. So does this mean that fingolimod and or siponimod may be useful for progressive MS. The studies are ongoing.