Name of Fellow

    Prof. dr. L.H. van den Berg




    Contact information of fellow


    The Netherlands

    Title of project/programme

    Amyotrophic lateral sclerosis: disease or syndrome?

    Source of funding information


    Total sum awarded (Euro)

    € 1,500,000

    Start date of award


    Total duration of award in years


    The project/programme is most relevant to:

    Motor neurone diseases


    amyotrophic lateral sclerosis | motor neuron disease | genetics | neuroimaging | heterogeneity

    Research Abstract

    Amyotrophic Lateral Sclerosis is usually described as a progressive disorder of upper- and lower
    motor neurons leading to muscle weakness and death due to respiratory failure on average 3 years
    after the onset of symptoms. In clinical practice, however, we experience a large variability in the
    clinical expression of the disease. An important gap in our knowledge of ALS pathophysiology is
    whether motor neurons in ALS die from a complex interaction between multiple factors or from the
    manifestation of a unique cause. In other words, is ALS one disease or just a phenotype of a large
    number of diseases with many causes? Filling this gap in knowledge may have important
    consequences for molecular diagnostic and therapeutic strategies in ALS and possibly other
    complex/neurodegenerative diseases. My working hypothesis is that ALS should be considered either
    as a collection of single, unique rare diseases or a diagnostic continuum in which ALS can be subclassified
    according to the relative contribution of genetic, environmental/lifestyle and phenotypic
    factors. I propose to establish the largest population-based case-control study of >2500 incident ALS
    patients and >5000 controls to determine phenotypic variability, genetic/environmental/lifestyle
    susceptibility and disease-modifying factors. I plan to discover additional ALS associated genes by
    applying (1) whole genome sequencing techniques in genetically unexplained familial ALS patients,
    and (2) a novel study design that, using imputation approaches, can then take advantage of discovered
    variants from whole genome sequence data from a subset of ALS patients, to infer untyped rare
    variants in the in my laboratory available datasets from previous GWAS. By using sophisticated
    exploratory cluster techniques, where multiple data modalities (phenotypic, neuroimaging,
    environmental/lifestyle, genetic) serve as input, subgroups will be identified. The results of this VICI
    research line may yield new insights in pathways underlying ALS and give leads for improved
    treatment of patients suffering from ALS.

Types: Fellowships
Member States: Netherlands
Diseases: Motor neurone diseases
Years: 2016
Database Categories: N/A
Database Tags: N/A

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