The Team
  • Researchers

    Mathieu ANHEIM

    Hélène PUCCIO

    Christine TRANCHANT


  • Post-Doctoral Fellows

    Olivier GRISO


  • PhD Students

    Ioannis MANOLARAS

  • Engineers & Technicians

    Nadège DIEDHIOU

    Aurélie EISENMANN

    Antoine HACHE

  • Collaborateur Occasionnel

    Laurence REUTENAUER

Translational medicine and neurogenetics

Fundamental and pathophysiological mechanisms implicated in ataxia

Hereditary ataxias are a heterogeneous set of severely disabling neurological disorders caused by degeneration of the cerebellum and/or the spinal cord. The prevalence of hereditary ataxias is estimated to 1/20,000 individuals in Europe, and yet there are no specific treatments for most of them.

Our research focuses on understanding the pathophysiology of ataxia, discovering disease biomarkers and developing therapeutic approaches. In addition, in close collaboration with the clinicians, we are developing new diagnostics tools for cerebellar ataxia and identify novel genes causing ataxia.

We are mainly interested in three different inherited ataxias: two recessive ataxias, Friedreich ataxia (FA) and autosomal recessive cerebellar ataxia 2 (ARCA2), linked to two essential mitochondrial pathways: iron-sulfur cluster (ICS) biosynthesis and coenzyme Q10 (CoQ10) biosynthesis, respectively; one dominant spinocerebellar ataxia, SCA7, a representative of the polyglutamine (polyQ) diseases, linked to the transcriptional regulation. FA and SCA7 belong to the family of trinucleotide repeat disorders, which are caused by dynamic mutations that show instability (expansion/contraction) in the germline and in selective somatic cells.


Friedreich ataxia (FA), the most common recessive ataxia, is characterized by progressive gait and limb ataxia associated with hypertrophic cardiomyopathy and an increase incidence in diabetes. The major mutation is a GAA repeat expansion within the first intron of the FXN gene. In FA, the GAA expansion leads to heterochromatinization of the locus resulting in a drastic decrease of transcription of FXN. The disease results from loss of function of FXN gene product, frataxin, a highly conserved mitochondrial protein involved in the biogenesis of ISC, which are essential protein cofactors implicated in numerous cellular functions.


The autosomal recessive cerebellar ataxia 2 (ARCA2) is characterized by cerebellar ataxia and atrophy, and is associated with exercise intolerance. Most patients present a mild deficiency in CoQ10 in muscle biopsies. ARCA2 results from loss of function mutations in the ADCK3/COQ8A gene that encodes a mitochondrial protein with a regulatory role in CoQ10 biosynthesis.


The dominant spinocerebellar ataxia 7 (SCA7) belongs to a group of neurodegenerative disorders caused by the abnormal expansion of polymorphic CAG repeats, leading to the toxic elongation of polyQ stretches in the corresponding disease proteins. These diseases include Huntington's disease and 5 other types of spinocerebellar ataxia (SCA1, 2, 3, 6, 17). SCA7 is due to polyQ expansion in the ataxin-7, a subunit of the transcriptional co-activator complex SAGA. SCA7 has a unique feature among polyQ diseases to cause retinal degeneration.

  • Current projects

    The current project of the team are the following:

    I.          Towards increasing diagnostics for cerebellar ataxia and identification of novel genes

    Combining clinical and genetic expertise, we are developing new diagnostics tools and identify novel genes for cerebellar ataxia. We are performing next generation sequencing to find new genes in cohorts of recessive cerebellar ataxia as well as sporadic late onset cerebellar ataxias. All new candidate genes are validated by functional studies.


    II.         Towards a better understanding of the pathophysiology of Friedreich Ataxia (FA), Cerebellar ataxia with CoQ10 deficiency (ARCA2) and spinocerebellar ataxia type 7 (SCA7)

    Our goals are to better define the function of the disease proteins and to decipher the cellular and molecular pathways involved in the diseases. We are studying faithful mouse, zebrafish and cell model of the diseases, using a wide range of techniques from biochemistry  and Omics (transcriptomic, epigenomic, proteomic, metabolomics) to functional and behavioural analyses.


    III.        Identification and validation of biomarkers for FA, ARCA2 and SCA7

    We aim at investigating in a systematic manner the blood and plasma composition along disease progression in mouse models and in patients using high-throughput technics. The detection of these alterations in circulating fluids provides an opportunity to identify and establish relevant biomarkers of disease onset and progression.


    IV.        Developing pre-clinical therapeutic approaches

    To pinpointing therapeutic targets, we are developing in vitro and cell-based high-throughput screening (HTS) strategies, to identify novel genes, pathways or drugs targeting sophisticated readouts, specifically tailored for FA, ARCA2 and SCA7. We profit of our panel of in vivo disease models to validate and further assess the promising targets. In parallel, advance candidate drugs, including gene therapy approaches, are directly tested in our already established mouse models using quantitative phenotypic parameters.

  • Collaborations

    • P. Aubourg and N. Cartier (St Vincent de Paul Hospital, Paris)
    • C. Bouton (Institut de Chimie des Substances Naturelles, Gif sur Yvette)
    • R. Festenstein (Imperial College London, London, UK)
    • J. Fontecilla and Y. Nicolet (Institut de Biologie Structurale, Grenoble)
    • M. Hentze and B. Galy (EMBL, Heidelberg, Germany)
    • D. R. Lynch (Philadelphia, USA)
    • R. Mendel and F. Bittner (Braunschweig, Germany)
    • A. Munnich and A. Rötig (Necker Hospital, Paris)
    • S. Ollagnier de Choudens (CEA, Grenoble)
    • M. Pandolfo (Brussels, Belgium)
    • F. Pierrel (CEA, Grenoble)
    • H. Puy (Centre Français des Porphyries, Paris)

  • Prizes/Awards

    • Hélène Puccio - Prix Antoine Lacassagne - Collège de France - 2016
    • Hélène PUCCIO - Scientific award - Académie Rhénane - 2014
    • Stéphane SCHMUCKER - Thesis Prize - Société de Biologie de Strasbourg - 2010
    • Alain MARTELLI - Young Investigator Award - National Ataxia Foundation - 2010
    • Hélène PUCCIO - Dr. Jean Toy Prize - Institut de France de l'Académie des Sciences - 2008
    • Stéphane SCHMUCKER - Jean-Claude Stoclet Prize - Faculté de Pharmacie de Strasbourg - 2008
    • Hélène PUCCIO - ERC Starting grant - European Research Council (ERC) - 2007
    • Hélène PUCCIO - Pediatric Pathology Research Senior Prize - Association pour l'Etude de la Pathologie Pédiatrique - 2004
    • Hélène PUCCIO - Young Investigator Award - National Ataxia Foundation - 2003
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