T-cells svar vid diagnos av amyotrofisk lateralskleros förutsäger sjukdomsförloppet

Amyotrophic lateral sclerosis (ALS) is devastating neurodegenerative disorder that in lack of effective treatments leads to death within a few years of diagnosis. ALS is increasingly recognized as a systemic disease affecting not only the nervous system but also other physiological aspects. We hypothesize that there is a disease-specific interplay between metabolism, gut microbiome and adaptive immunity that substantially contributes to the etiology of ALS. Our aim is therefore to explore such interplay, and to assess the effectiveness of a treatment regimen that specifically targets it. Using a population-based case-control study, we will first characterize the complex interactions between metabolism, microbiome, and immunity in ALS, through comprehensive proteomic, metagenomic and immune-response profiling. We will then use established ALS disease models to understand the usefulness of combining a high-caloric diet with a fecal microbiota transplant in disease prevention and treatment. The proposed research is unique as it 1) combines innovative molecular platforms with a high-quality epidemiological study design, 2) uses a novel strategy of investigating multiple aspects of human physiology, and 3) offers a possibility to directly translate findings between human observational and animal experimental studies. The ultimate goal is to advance our knowledge about ALS as a disease, and to identify novel and highly warranted preventive and therapeutic targets for it.