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Unravelling the Interplay between Metabolism, Gut Microbiome and Adaptive Immunity in Amyotrophic Lateral Sclerosis

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.

Field of science

  • /medical and health sciences/basic medicine/neurology/amyotrophic lateral sclerosis
  • /medical and health sciences/basic medicine/physiology

Call for proposal

ERC-2018-STG
See other projects for this call

Funding Scheme

ERC-STG - Starting Grant

Host institution

KAROLINSKA INSTITUTET
Address
Nobels Vag 5
17177 Stockholm
Sweden
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 499 196

Beneficiaries (1)

KAROLINSKA INSTITUTET
Sweden
EU contribution
€ 1 499 196
Address
Nobels Vag 5
17177 Stockholm
Activity type
Higher or Secondary Education Establishments