Heesen, C. | bioRxiv Science

bioRxiv2018

Short-term aerobic training does not improve memory functioning in relapsing remitting multiple sclerosis - a randomized controlled trial

BackgroundOnly few aerobic exercise intervention trials specifically targeting cognitive functioning have been performed in MS.\n\nObjective and methodsThis randomized controlled trial aimed to determine the effects of aerobic exercise on cognition in relapsing-remitting MS. The primary outcome was verbal memory (Verbal learning and memory test, VLMT). Patients were randomized to an intervention group (IG) program or a waitlist control group (CG). Patients in the IG exercised according to an individually tailored training schedule (with 2-3 sessions per week for 12 weeks). The primary analysis was carried out using the intention-to-treat (ITT) sample with ANCOVA adjusting for baseline scores.\n\nResults77 RRMS patients were screened and 68 participants randomized (CG n=34; IG n=34). The sample comprised 68% females, had a mean age of 39 years, a mean disease duration of 6.3 years, and a mean EDSS of 1.8. No significant effects were detected in the ITT analysis for the primary endpoint VLMT or any other cognitive measures. Moreover, no significant treatment effects were observed for quality of life, fatigue, or depressive symptoms.\n\nConclusionThis study failed to demonstrate beneficial effects of aerobic exercise on cognition in RRMS.\n\nThe trial was prospectively registered at clinicaltrials.gov (NCT02005237).

clinical trials↗

bioRxiv2018

Low frequency and rare coding variation contributes to multiple sclerosis risk

Multiple sclerosis is a common, complex neurological disease, where almost 20% of risk heritability can be attributed to common genetic variants, including >230 identified by genome-wide association studies (Patsopoulos et al., 2017). Multiple strands of evidence suggest that the majority of the remaining heritability is also due to the additive effects of individual variants, rather than epistatic interactions between these variants, or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that as much as 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common variant signals, which highlight a key role for regulatory T cell homeostasis and regulation, IFN{gamma} biology and NF{kappa}B signaling in MS pathogenesis. As low-frequency variants do not show substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS.

genetics↗