Project description
Insight into the role of metabolism and immunity in ALS
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that also affects other systems apart from the central nervous system. The EU-funded MegaALS is investigating the hypothesis that the interplay between metabolism, gut microbiome and adaptive immunity drives ALS pathophysiology. Scientists are using proteomic, metagenomic and immune-response data from a population-based case-control study of ALS in Stockholm to validate this hypothesis. Moreover, they will employ an ALS mouse model to test an innovative disease prevention and treatment strategy that combines a high-caloric diet with a faecal microbiota transplant from healthy human donors. Results will unveil the pathophysiological mechanisms of ALS and identify novel preventive and therapeutic targets.
Objective
Amyotrophic lateral sclerosis (ALS) is a rare but devastating neurodegenerative disorder that in lack of effective treatments leads to death within a few years of diagnosis. ALS is increasingly being recognized as a systemic disease affecting not only the central nervous system but also other physiological aspects. We hypothesize that there is a disease-specific interplay between metabolism, gut microbiome and adaptive immunity, which substantially contributes to the etiopathogenesis of ALS. The overarching aim of this project 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 of ALS in Stockholm, I will first characterize the complex interactions between metabolism, microbiome, and immunity in ALS, through comprehensive proteomic, metagenomic and immune-response profiling. The specificity of these interactions will be tested in contrast to healthy individuals at high risk for ALS (siblings), individuals with similar environmental and lifestyle factors (spouses), and unrelated population-controls. I will then use an established ALS mouse model (SOD1G93A) to understand the usefulness of combining a high-caloric diet with a fecal microbiota transplant from healthy human donors in disease prevention and treatment. To better understand the underlying mechanisms, I will compare microbiome and immune-response profiles before and after the intervention. 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 significantly advance our knowledge about ALS as a disease, and more importantly to identify novel and highly warranted preventive and therapeutic targets.
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Funding Scheme
ERC-STG - Starting GrantHost institution
17177 Stockholm
Sweden