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Introduction: Immune activation has been implicated in progression of amytrophic lateral sclerosis (ALS). Oral fingolimod reduces circulating lymphocytes. The objective of this phase IIa, randomized, controlled trial was to test the short-term safety, tolerability, and target engagement of fingolimod in ALS.Methods: Randomization was 2:1 (fingolimod:placebo). Treatment duration was 4 weeks. Primary outcomes were safety and tolerability. Secondary outcomes included circulating lymphocytes and whole-blood gene expression.Results: Thirty participants were randomized; 28 were administered a drug (fingolimod 18, placebo 10). No serious adverse events occurred. Adverse events were similar by treatment arm, as was study discontinuation (2 fingolimod vs. 0 placebo, with no statistical difference). Forced expiratory volume in 1 second (FEV1 ) and FEV1 /slow vital capacity changes were similar in the fingolimod and placebo arms. Circulating lymphocytes decreased significantly in the fingolimod arm (P < 0.001). Nine immune-related genes were significantly downregulated in the fingolimod arm, including forkhead box P3 (P < 0.001) and CD40 ligand (P = 0.003).Discussion: Fingolimod is safe and well-tolerated and can reduce circulating lymphocytes in ALS patients. Muscle Nerve 56: 1077-1084, 2017. [ABSTRACT FROM AUTHOR]

In order to assess whether disclosure of emotions through writing about upsetting or traumatic events resulted in changes in blood-associated immune variables over time, healthy volunteers were randomly assigned to write about either emotional issues or trivial topics for 4 consecutive days. Circulating lymphocytes and T lymphocyte subsets (CD4 (helper). CD8 (cytotoxic/suppressor)) as well as a variety of standard hematological markers were measured following the writing intervention and compared with baseline values. In two separate studies (N - 40 and N 38), there were reproducible significant differences between the emotional disclosure and control writing groups immediately following the intervention in CD4. CDS and total circulating lymphocyte numbers but not in CD4/CD8 ratios or any other hematological variables. Circulating lymphocyte numbers in the emotional writing group stayed relatively constant over the time-course of the studies, suggesting that the difference between the groups was due to a transient elevation in postwriting blood lymphocyte numbers in the control group. Self-evaluations immediately before and after each writing session confirmed that the intervention was stressful for subjects in the emotional disclosure group hut the effects on circulating lymphocytes were not attributable purely to anxiety-related factors. The results extend our previous observation of changes in immune reactivity following a writing intervention and indicate that the group differences are the result of fluctuations over time in the control group but relative stability in the emotional disclosure groups It is conceivable that such 'buffering' of temporal immune variation might be influential in the health-promoting effects of emotional disclosure. [ABSTRACT FROM AUTHOR]