Principal Investigators

    Dr. ir. M.J.W. Adjobo-Hermans


    Radboud Universiteit Nijmegen

    Contact information of lead PI



    Title of project or programme

    Advancing the European Multidisciplinary Initiative on Neuroacanthocytosis - EMINA-2: Dissecting the molecular pathophysiology of Chorea-Acanthocytosis

    Source of funding information


    Total sum awarded (Euro)

    € 250,000

    Start date of award


    Total duration of award in years



    Research Abstract

    Neuroacanthocytosis (NA) syndromes are a group of rare disorders displaying neurodegeneration and misshaped spiky red
    blood cells (acanthocytes). NA syndromes include Chorea-acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington’s
    disease-like 2, and pantothenate kinase-associated neurodegeneration (PKAN) with ChAc as the prototype of this disease
    family. The European Multidisciplinary Initiative on Neuroacanthocytosis (EMINA-1) funded by the E-Rare-program 2009
    provided detailed clinical characterization of the different NA syndromes and collected valuable brain and muscle tissue
    samples of ChAc patients. ChAc is caused by loss-of-function mutations within the gene VPS13A encoding for a protein of
    unknown function named Chorein. Within the EMINA-1 initiative, we recently found two signalling kinases as involved in ChAc
    pathogenesis, but its exact pathophysiology remains enigmatic.
    Based on the successful EMINA-1 network, the EMINA-2 consortium brings together 5 Young Investigators from leading
    European laboratories in the fields of human cell models (induced pluripotent stem [iPS] cells), neurodegeneration, erythrocyte
    biology, as well as murine and Drosophila ChAc models with the aim to explore in depth the molecular pathophysiology of
    ChAc and translate this knowledge into new curative therapeutic approaches. Together we will combine our complementary
    expertise involving molecular genetics, cell biology and protein biochemistry, neurophysiology and behavioural studies to
    address how loss-of-function of VPS13A/Chorein translates into neurodegeneration and erythrocyte pathology with focus on
    alterations of intracellular signalling cascades and their cross-talk to cytoskeleton function. We will use human iPS cells,
    VPS13A knockout mice and mutant Drosophilae as ChAc models as well as patient materials generated by EMINA-1. The new
    knowledge that we will acquire will provide us with potential drug targets for compound library screening with our Drosophila
    ChAc models seeking to identify efficacious treatments to be explored in mammalian and human models. Since ChAc can be
    seen as paradigmatic disorders to study the reasons for selective vulnerability of specific cell types, the results of EMINA-2 will
    help to understand other diseases affecting erythrocytes membrane physiology and basal ganglia circuitries.

    Further information available at:

Types: Investments < €500k
Member States: Netherlands
Diseases: N/A
Years: 2016
Database Categories: N/A
Database Tags: N/A

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