HUNTINGTON

In vitro

  • hES from control and affected patients with Huntingtin mutations (different lengths of CAG triplet): differentiation into cortical / striatal neurons
  • iPS cells from control and affected patients with Huntingtin mutations (different lengths of CAG triplet): cell lines from fibroblasts could be differentiated into cortical / striatal neurons or glial cells.
  • Primary cortical or striatal neuron cultures with or without astrocytes
  • Primary cortical or striatal neuron cultures of neurons infected with AAV or LV vectors coding huntingtin gene (different lengths of CAG triplet)
Read-out
Cell survival, morphological changes, protein measurement, etc.

Rodents

  • Striatal cell degeneration: injections of quinolinate (or other glutamate agonists) or chronic systemic 3NP
  • Transgenic models of progressive degeneration (KI140CAG mouse, BACHD rat)
  • Progressive striatal degeneration: injection of lentiviral /AAV vectors encoding fragments of mutated huntingtin gene
Read-out
Neuroinflammation and glucose metabolism PET imaging, MRI, MR spectroscopy, 3D -histology, motor and cognitive behavior, etc.

Non-human primates

  • Excitotoxic striatal lesions (Macaque): injections of quinolinate (or other glutamate agonists) or chronic systemic 3NP
  • Progressive striatal degeneration: injection of lentiviral /AAV vectors encoding fragments of mutated huntingtin gene
Read-out
Neuroinflammation and glucose metabolism PET imaging, MRI, MR spectroscopy, histology, motor and cognitive behavior, etc.

Humans

  • Clinical investigation Center, Biological resource center, neurology units, stratified cohorts of patients, coordination of the French National Reference Centre for Huntington's disease and the Huntington's disease group of the European Network for Rare Diseases
Read-out
PET and MRI imaging, Markers of dopaminergic system and neuroinflammation, platforms of movement analysis, specific cognitive tools
A comprehensive overview of our offer in the field of HUNTINGTON disease:
  • Basic Research

    Cellular models

    In-vitro cell culture (primary cell cultures) of (mouse/rat) cortical and/or striatal neurons

     - Evaluation (through quantification of neuronal survival) of the properties of new molecules in a cell death model induced by different neurotoxins (quinolinate, glutamate, 3-nitropropionate), leading to oxidative stress, mitochondrial impairment and excitotoxicity.

    - Evaluation (through quantification of neuronal survival) of the effects of new molecules in a cell death model induced by injection lentiviral vectors encoding different parts of the mutated huntingtin gene.

    - Evaluation (through quantification of neuron survival) of the properties of new molecules in a spontaneous cell death model obtained from primary cell cultures (neurons/astrocytes) arising from transgenic mouse models of Huntington’s disease

    In-vitro model of human ESC and/or iPS cells obtained from HD patients

    - In vitro differentiation of cell lines issued from patients bearing different CAG repeats and from healthy controls

    - Identification of cell death events or mechanisms of cellular dysfunction at play in these cells to identify potential new therapeutic targets

    - Evaluation (through quantification of neuronal survival) of new drug- or gene-based strategies in this cell death model induced by different neurotoxins, ), leading to oxidative stress, mitochondrial impairment and apoptosis.

    Animal models

    Rodent Models (mouse, rat)

    In vivo rodent Models of striatal cell degeneration induced by neurotoxins

    Excitotoxic striatal lesions in rat or mice induced by intrastriatal stereotactic injections of quinolinate (or otherglutamate agonists)

    - Evaluation of the neuronal cell death, neurochemical deficits, motoric alterations, and neuroinflammation induced in these models,

    - Evaluation of potential neuroprotective effects of drug- or gene-based therapeutic strategies on these models,

    - Evaluation of potential neurorestorative strategies (cell-, gene- or drug-based) on motor symptoms in chronically lesioned animals

    - Development of new imaging modalities for the in vivo monitoring of various disease processes (neuro-inflammation, cell death markers, etc...)

    Chronic systemic 3NP lesion model

    - Longitudinal evaluation of potential neuroprotective strategies (either drug- or gene-based)

    - Longitudinal evaluation of neurorestorative strategies (either cell-, gene- or drug-based) on motor symptoms in chronically lesioned animals

    - follow-up of symptoms in chronically lesioned animals

    - Development of new imaging modalities for the in vivo monitoring of various disease processes (neuro-inflammation, cell death markers, etc...)

    Genetic Models

    Rodent (mouse/rat) models of progressive striatal degeneration induced by local injection of viral vectors (AAV/lentivirus) encoding various fragments of the mutated huntingtin gene

    - Evaluation of neuroprotectrice strategies (drug-based, gene-based) through biochemical, transcriptomics and histological approaches

    - Development of new imaging modalities for the in vivo monitoring of various disease processes (neuro-inflammation, cell death markers, etc...)

    Transgenic models of progressive degeneration and dysfunction in mouse (for example, the KI140CAG model)

    - Evaluation of neuroprotectrice strategies (drug-based, gene-based) through biochemical, transcriptomics and histological approaches

    - Development of new imaging modalities for the in vivo monitoring of various disease processes (neuro-inflammation, cell death markers, etc...)

     

    Lentiviral and/or AAV vectors to obtain proof of concept on potential therapeutic targets in different genetic models of Huntington’s disease

     

    Basic research tools available

    Biochemistry and Proteomics

    - « Western blot » Quantitative Analyses

    - ELISA

     

    Transcriptomics

    - MicroArray

    - RNA seq

     

    Microscopy

    - Real time video-microscopy

    - Robotized epifluorescence microscopy

    - Confocal microscopy

  • Preclinical Research
  • Clinical Research