In-depth analysis of data from the RAS-ALS study reveals new insights in rasagiline treatment for amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In 2016, we concluded a randomized controlled trial testing 1 mg rasagiline per day add-on to standard therapy in 252 amyotrophic lateral sclerosis (ALS) patients. This article aims at better characterizing ALS patients who could possibly benefit from rasagiline by reporting new subgroup analysis and genetic data. METHODS: We performed further exploratory in-depth analyses of the study population and investigated the relevance of single nucleotide polymorphisms (SNPs) related to the dopaminergic system. RESULTS: Placebo-treated patients with very slow disease progression (loss of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R] per month before randomization of ≤0.328 points) showed a per se survival probability after 24 months of 0.85 (95% confidence interval = 0.65-0.94). The large group of intermediate to fast progressing ALS patients showed a prolonged survival in the rasagiline group compared to placebo after 6 and 12 months (p = 0.02, p = 0.04), and a reduced decline of ALSFRS-R after 18 months (p = 0.049). SNP genotypes in the MAOB gene and DRD2 gene did not show clear associations with rasagiline treatment effects. CONCLUSIONS: These results underline the need to consider individual disease progression at baseline in future ALS studies. Very slow disease progressors compromise the statistical power of studies with treatment durations of 12-18 months using clinical endpoints. Analysis of MAOB and DRD2 SNPs revealed no clear relationship to any outcome parameter. More insights are expected from future studies elucidating whether patients with DRD2CC genotype (Rs2283265) show a pronounced benefit from treatment with rasagiline, pointing to the opportunities precision medicine could open up for ALS patients in the future.

Interoceptive accuracy is associated with benefits in decision making in children.

Introduction: Decision making results not only from logical analyses, but seems to be further guided by the ability to perceive somatic information (interoceptive accuracy). Relations between interoceptive accuracy and decision making have been exclusively studied in adults and with regard to complex, uncertain situations (as measured by the Iowa Gambling Task, IGT). Methods: In the present study, 1454 children (6-11 years) were examined at two time points (approximately 1 year apart) using an IGT as well as a delay-of-gratification task for sweets-items and toy-items. Interoceptive accuracy was measured using a child-adapted version of the Heartbeat Perception Task. Results: The present results revealed that children with higher, as compared to lower, interoceptive accuracy showed more advantageous choices in the IGT and delayed more sweets-items, but not toy-items, in a delay-of-gratification task at time point 2 but not at time point 1. However, no longitudinal relation between interoceptive accuracy and decision making 1 year later could be shown. Discussion: Results indicate that interoceptive accuracy relates to decision-making abilities in situations of varying complexity already in middle childhood, and that this link might consolidate across the examined 1-year period. Furthermore, the association of interoceptive accuracy and the delay of sweets-items might have implications for the regulation of body weight at a later age.