Search for Potential Biomarkers at Baseline in a Large ALS Cohort Study (ALS COSMOS): Plasma Creatinine and Urinary 8-oxo-deoxyguanosine. (P5.054)

Objective: To evaluate multiple potential biomarkers in ALS. Background: Reliable biomarkers in ALS are needed in ALS clinical trials and other studies to quantify disease severity and progression. Multiple biomarkers have seldom been investigated Design/Methods: In a large (355 patients), prospective, cohort study, plasma samples at baseline were obtained after overnight fasting, and first morning void spot urine samples were collected and adjusted for dilution using specific gravity. Broad lipid profiles, creatinine (PCr), paraoxonase 1 (PON1) activity and genotype status, phosphorylated neurofilament heavy, urinary 8-oxo-deoxyguanosine (8-oxo-dG), and urinary isoprostane (IsoP) were measured as part of the baseline evaluation. ALSFRS-R and predicted [percnt]forced vital capacity ([percnt]FVC) were used to assess severity. Results: Mean (standard deviation (SD)) value for 8-oxo-dG was 17.1 (13.8) nmol/mmol and mean (SD) value for PCr was 0.80 (0.20) mg/dL. Both 8-oxo-dG and PCr were independently associated with ALSFRS-R and [percnt]FVC. The regression models were adjusted for age, sex and other key variables. For each unit increase in 8-oxo-dG, ALSFRS-R decreased by 0.11 points (p = .0064) and for each .1 unit increase in PCr, ALSFRS-R increased by 0.88 points (p< .0001). 8-oxo-dG and PCr were weakly and negatively correlated (Spearman’s r = -.12; p = .025). When both 8-oxo-dG and PCr were included in the same regression model, the point estimates decreased slightly but remained statistically significant, consistent with a partial mediation effect. None of the other biomarkers showed correlations with the clinimetric data. Conclusion: PCr and 8-oxo-dG are independently associated with ALSFRS-R and [percnt]FVC at baseline. The association between 8-oxo-dG and the outcomes may be partially mediated by PCr. These are promising biomarkers for assessment of ALS severity based on baseline data and we will soon have longitudinal data on progression available. (Funded by NIH R01ES016348, MDA, MDA Wings, and others) Disclosure: Dr. Mitsumoto has nothing to disclose. Dr. Santella has nothing to disclose. Dr. Hupf has nothing to disclose. Dr. Furlong has nothing to disclose. Dr. Cremers has nothing to disclose. Dr. Votto has nothing to disclose. Dr. Singleton has nothing to disclose. Dr. Goetz has nothing to disclose. Dr. Gurvich has nothing to disclose. Dr. Oskarsson has received personal compensation for activities with Avanir Pharmaceuticals as a speaker. Dr. Fernandes-Filho has nothing to disclose. Dr. Gennings has nothing to disclose. Dr. Factor-Litvak has nothing to disclose.