Descripción del proyecto
Información sobre la función del metabolismo y la inmunidad en la ELA
La esclerosis lateral amiotrófica (ELA, o ALS por sus siglas en inglés) es un trastorno neurodegenerativo que afecta no solo al sistema nervioso central, sino también a otros sistemas. En el proyecto MegaALS, financiado con fondos europeos, se investiga la hipótesis de que la interacción entre el metabolismo, el microbioma intestinal y la inmunidad adaptativa sustente la fisiopatología de la ELA. Para validar esta hipótesis, los científicos están utilizando los datos proteómicos, metagenómicos y de respuesta inmunitaria de un estudio de casos y controles basado en la población con ELA en Estocolmo. Además, emplearán un modelo murino de ELA para probar una estrategia innovadora para prevenir y tratar la enfermedad, que combina una dieta de alto contenido calórico con un trasplante de microbiota fecal de donantes humanos sanos. Los resultados revelarán los mecanismos fisiopatológicos de la ELA e identificarán nuevos objetivos de prevención y tratamiento.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
17177 Stockholm
Suecia