Increase of arginine dimethylation correlates with the progression and prognosis of ALS.

Objective: To investigate whether arginine methylation is altered in patients with amyotrophic lateral sclerosis (ALS) and how it affects disease severity, progression, and prognosis.
Methods: We compared the immunoreactivity of protein arginine methyltransferase 1 (PRMT1) and its products, asymmetric dimethylated proteins (ASYM), in postmortem spinal cord. We also measured the concentrations of total l-arginine and methylated arginine residues, including asymmetric dimethyl l-arginine (ADMA), symmetric dimethyl arginine, and monomethyl arginine, in CSF samples from 52 patients with ALS using liquid chromatography-tandem mass spectrometry, and we examined their relationship with the progression and prognosis of ALS.
Results: The immunoreactivity of both PRMT1 ( p < 0.0001) and ASYM ( p = 0.005) was increased in patients with ALS. The concentration of ADMA in CSF was substantially higher in patients with ALS than in disease controls. The ADMA/l-arginine ratio was correlated with the change of decline in the ALS Functional Rating Scale at 12 months after the time of measurement ( r = 0.406, p = 0.010). A Cox proportional hazards model showed that the ADMA/l-arginine ratio was an independent predictor for overall survival. Moreover, a high ADMA/l-arginine ratio predicted poor prognosis, even in a group with normal percentage forced vital capacity.
Conclusion: There was an enhancement of arginine dimethylation in patients with ALS, and the ADMA/l-arginine ratio predicted disease progression and prognosis in such patients.
(© 2019 American Academy of Neurology.)