Cerebrospinal Fluid S-Adenosyl Methionine Levels are Decreased in Multiple Sclerosis Patients

Objective: To investigate the involvement of S-Adenosyl methionine (SAM) in the pathophysiology of multiple sclerosis (MS). Background: S-Adenosyl methionine (SAM) is a major methyl group donor to various substrates such as nucleic acids, proteins, phospholipids, neurotransmitters and secondary metabolites. SAM thus regulates a variety of cellular processes including DNA, tRNA, and rRNA methylation; immune response; amino acid metabolism; and transsulfuration. . Transmethylation reactions convert SAM into S-adenosylhomocysteine (SAH), the latter being a potent inhibitor of methylation. The SAM/SAH ratio has been used to measure the methylation potential of a cell. Design/Methods: Cerebrospinal fluid (CSF) was obtained from MS patients (n = 43) and controls (n = 12) with informed consent under an IRB-approved protocol. Samples were immediately processed and stored at -80 degree until use. SAM and SAH levels in CSF were measured by ELISA (Cell Biolabs. Inc.). Data obtained was analyzed using Graphpad Prism. Methionine metabolites were also quantified by mass spectrometry (AbsoluteIDQ p180, Biocrates, Austria). Results: We found significantly lower levels of SAM in the CSF of MS patients as compared to levels in control subjects (p = 0.013). Furthermore, we found a trend towards concomitant increased in SAH levels in the MS cohort as compared to controls. Interestingly within the MS patient population, a significantly higher SAM/SAH ratio was found to be associated with active disease. In a parallel metabolomic screen, we also found decreased amount of methionine in the CSF of MS patients. Conclusions: These results show a disruption of the SAM metabolism in MS, which may have significant implications on DNA methylation, myelination as well as the levels of the anti-oxidant glutathione. Further investigation will help elucidate whether these findings are related to the pathophysiology of the disease Study Supported by: Tisch Multiple Sclerosis Research Center Internal Funds

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