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Clinical research at MIRCen

Recherche clinique à MIRCen
Published on 3 July 2018

The research teams of MIRCen collaborate closely with the clinical imaging center of Frédéric Joliot Hospital (SHFJ), one of the departments of the Institute of Biomedical Imaging, and the departments of neurology and neurosurgery of Henri Mondor Hospital (Paris XI University). These collaborations are developing innovative treatments for neurodegenerative diseases in the framework of a translational approach. 

PET, SPECT and PET/MRI at the SHFJ

  • A 15 MeV cyclotron for the production of positron emitters
  • Nonradioactive chemistry and radiochemistry laboratories for the preparation of radiopharmaceuticals in accordance with good manufacturing practice
  • Three positron emission tomographs, including a system with very high spatial resolution for brain imaging
  • A system for bimodal PET and TDM (tomodensitometry) imaging
  • Two gamma cameras for scintigraphy and single-photon emission computed tomography (SPECT)
  • A 1.5 T MRI system
  • A set of tools for advanced image processing, including pharmacokinetic modeling and multimodal image analysis
  • Four day-hospital rooms

Crédit : P.Stroppa/cea


RESEARCH

Our team is composed of Sonia Lavisse (CEA researcher) and Véronique Gaura (neurologist and nuclear physician at the Thenon hostpital). Our team specializes in the use of functional imaging to advance towards two objectives:

  1. the identification of diagnostic markers or markers of the progression of neurodegenerative diseases (=biomarkers)
  2. the exploitation of these markers to study the effects of innovative treatments, such as biotherapies in particular, on these diseases.


This approach is made possible by the use of high-resolution imaging tools, the availability of radiotracers (cyclotron) at the SHFJ and access to cohorts of patients through collaboration with the teams at the Salpêtrière and Henri Mondor Hospitals.


Identification de Biomarqueurs

In the Parkinson’s disease, markers of dopaminergic neuron loss, the key feature of this condition, have long been used to assess disease progression. We have also studied other phenomena, such as abnormalities of nicotinic receptors, of this disease. We are currently investigating whether inflammatory processes contribute to neuron cell death in this disease, using a tracer likely to provide evidence of such processes in the zones in which neuron death occurs.

We are also exploring the phenotype of subjects carrying a mutation (LRRK2) that may cause Parkinson’s disease, to determine the duration of the preclinical phase of the disease and to identify markers of this phase

For Huntington’s disease, we use the classical markers of progression of this disease: morphological abnormalities on MRI (e.g. striatal atrophy, figure 1) or decreases in metabolism and in the density of striatal D2 receptors


These research activities are in close collaborations with the Mondor Hospital and in particular :

  • Pr Anne Catherine Bachoud Lévi, head of the neurology department with expertise in the domain of neurodegenerative diseases (Parkinson, Alzheimer, multiple sclerosis) and national expert center for the Huntington Disease with large cohorts of patients. The research team of Pr Bachoud Lévi has strong skills in the cognitive aspects of neurodegenerative diseases (in particular language in collaboration with Ecole Normale Supérieure) and functional imaging (Pr Philippe Remy).
  • Pr Stéphane Palfi, head of the neurosurgery department equipped for stereotactic surgery and specializing in biotherapy (gene transfer and cell therapy)

  • A clinical investigation center for biotherapy


Results and major publications 

  • 20 years of experience with clinical brain imaging in patients with Parkinson's and Huntington's diseases (funding from the Ministry of Health and private foundations)
  • International expertise in the clinical transplantation of cells for Parkinson's and Huntington's diseases (Prof. Stéphane Palfi, Prof. Philippe Remy, Prof. Bachoud-Lévy)
  • First European clinical trial of gene therapy in vivo for Parkinson's disease, funded by Oxford Biomedica Ltd. (Prof. Stéphane Palfi, Prof. Philippe Remy, Clinical Imaging)
  • High-frequency cortical stimulation for the treatment of Parkinson's disease and movement disorders (Prof. Stéphane Palfi, Prof. Philippe Remy, Clinical Imaging)
  • Coordination of the national Huntington's disease network (Prof. Bachoud-Lévy).

Publications 


  • Association Between Motor Symptoms and Brain Metabolism in Early Huntington Disease
    Gaura V, Lavisse S, Payoux P, Goldman S, Verny C, Krystkowiak P, Damier P, Supiot F, Bachoud-Levi AC, Remy P. 
    JAMA Neurol. 2017 Sep 1;74(9):1088-1096
  • Optimized Quantification of Translocator Protein Radioligand ¹⁸F-DPA-714 Uptake in the Brain of Genotyped Healthy Volunteers.
    Lavisse S, García-Lorenzo D, Peyronneau MA, Bodini B, Thiriez C, Kuhnast B, Comtat C3 Remy P, Stankoff B, Bottlaender M
    J Nucl Med. 2015 Jul;56(7):1048-54
  • Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial.
    Palfi S, Gurruchaga JM, Ralph GS, Lepetit H, Lavisse S, Buttery PC, Watts C, Miskin J, Kelleher M, Deeley S, Iwamuro H, Lefaucheur JP, Thiriez C, Fenelon G, Lucas C, Brugières P, Gabriel I, Abhay K, Drouot X, Tani N, Kas A, Ghaleh B, Le Corvoisier P, Dolphin P, Breen DP, Mason S, Guzman NV, Mazarakis ND, Radcliffe PA, Harrop R, Kingsman SM, Rascol O, Naylor S, Barker RA, Hantraye P, Remy P, Cesaro P, Mitrophanous KA.
    Lancet. 2014 Mar 29;383(9923):1138-46. 
  • In vivo evidence for the selective subcortical degeneration in Huntington's disease.
    Douaud G, Behrens TE, Poupon C, Cointepas Y, Jbabdi S, Gaura V, Golestani N, Krystkowiak P, Verny C, Damier P, Bachoud-Lévi AC, Hantraye P, Remy P.
    Neuroimage. 2009 Jul 15;46(4):958-66. 
  • Language processing within the striatum: evidence from a PET correlation study in Huntington's disease.
    Teichmann M, Gaura V, Démonet JF, Supiot F, Delliaux M, Verny C, Renou P, Remy P, Bachoud-Lévi AC.
    Brain. 2008 Apr;131(Pt 4):1046-56. 
  • Distribution of grey matter atrophy in Huntington's disease patients: a combined ROI-based and voxel-based morphometric study.
    Douaud G, Gaura V, Ribeiro MJ, Lethimonnier F, Maroy R, Verny C, Krystkowiak P, Damier P, Bachoud-Levi AC, Hantraye P, Remy P.
    Neuroimage. 2006 Oct 1;32(4):1562-75. 
  • Effect of fetal neural transplants in patients with Huntington's disease 6 years after surgery: a long-term follow-up study.
    Bachoud-Lévi AC, Gaura V, Brugières P, Lefaucheur JP, Boissé MF, Maison P, Baudic S, Ribeiro MJ, Bourdet C, Remy P, Cesaro P, Hantraye P, Peschanski M.
    Lancet Neurol. 2006 Apr;5(4):303-9.