Research Laboratories

Inserm Unit U1234
Pathophysiology, Autoimmunity, Neuromuscular diseases and regenerative THERapies (PANTHER)

FOCIS Excellence Center Member


PANTHER


Head


Pr Olivier Boyer, Director
Pr Sophie Candon, Deputy Director
Chantal Barou, Administrative Officer


Contact


Research unit 1234 Inserm/University
Faculty of Medicine and Pharmacy
22 Boulevard Gambetta
76183 Rouen Cedex
Phone: +33 235 14 8535

chantal.barou@inserm.fr
olivier.boyer@chu-rouen.fr


Research Topics


  • Immuno-regulation
  • Physiology, pathophysiology, diagnosis and biotherapies
  • Autoimmunediseases
  • Cell and genetherapy

Composition


  • 41 scientists, professors, engineers, technicians
  • 9 PhD students
  • 6 Master students

Facilities


  • Flow cytometry core facility (FACSorting and single-cell analysis)
  • Virus-mediatedgenetransfer
  • In vivoexperimentalmodels
  • Development of immunologicalbioassays

Activity


The research program of Inserm U1234 focuses on the immunopathology and the biotherapy of autoimmune diseases. Autoimmunity and its regulation are studied in physiological and pathological contexts, through murine models and clinical studies in the field of neuromuscular (myositis, multiple sclerosis) and skin (pemphigus) diseases.

The program is divided into two thematic areas (A)
A1. The first one centers on the immuno-regulation by ectonucleotides (ATP, NAD) or by neuropeptides (VIP, PACAP), and pathophysiological mechanisms of autoimmune diseases (myositis, multiple sclerosis, pemphigus). It is based on the development and analysis of murine models (transgenic, knock-out, viral gene transfer) and clinical studies. Focus is put on inflammatory mechanisms, oxidative stress, pathogenicity of auto-antibodies from patients and autoreactive B cell responses at a single-cell level. Immuno-assays are developed and translated to the clinic.
A2. The second area has a therapeutic goal through the translation of cell and gene transfer strategies to clinical trials. This includes myoblast cell therapy, adipose-derived stem cell therapy, corneal tissue/cell transplantation and olfactory stem cells for neural regeneration.

Inserm U1234 is a founding member of the FHU SURFACE and part of the LARC neuroscience network.


Main Contributions


  • Demonstration of the pathogenic role of autoimmune antibodies in immune-mediated necrotising myopathy.
  • Evaluation and detailed immune-monitoring of B cell targeted therapies that changed the therapeutical strategies in autoimmune blistering skin diseases.
  • Development of unique immuno-assays for quantification of anti–SRP, anti-HMGCR and anti-TIF1gamma autoantibodies for improving patient diagnosis and understanding autoantibodies pathogenicity.
  • Development of clinical trials using adipose-derived stem cells.
  • Demonstration of the immune-regulatory role of extracellular nucleotides (ATP, NAD).
  • First detailed report on the genetic safety profile of clinical-grade human myoblasts and proof-of-principle of myoblast therapy for experimental striated sphincter insufficiency.
  • First randomized placebo-controlled myoblast clinical trial demonstrating efficacy of this cell therapy in fecal incontinence

Main Publications


2018

  • Abdoul-Azize S, Buquet C, Li H, Picquenot JM and Vannier JP. Integration of Ca2+ signaling regulates the breast tumor cell response to simvastatin and doxorubicin. Oncogene 2018, 37: 4979-4993.
    29795329
  • Bergua C, Chiavelli H, Allenbach Y, Arouche-Delaperche L, Arnoult C, Bourdenet G, Jean L, Zoubaïri R, Guérout N, Malher M, Benveniste O, Drouot L and Boyer O. vivo pathogenicity of IgG from patients with anti-SRP or anti-HMGCR autoantibody positive immune-mediated necrotising myopathy. Ann Rheum Dis 2018

2017

  • Bourdenet G, Dubourg B, Nicol L, Mulder P, Martinet J, Allenbach Y, Boitard C and Boyer O. Value of magnetic resonance imaging for evaluating muscle inflammation: insights from a new mouse model of myositis. Neuropathol Appl Neurobiol 2017
    29231968
  • Boyer O, Bridoux V, Giverne C, Bisson A, Koning E, Leroi AM, Chambon P, Déhayes J, Le Corre S, Jacquot S, Bastit D, Martinet J, Houivet E, Tuech JJ, Benichou J and Michot F; and the Study Group of Myoblast Therapy for Faecal Incontinence. Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase 2 Randomized Placebo-controlled Study (MIAS). Ann Surg 2017
    28426476
  • Abad C, Jayaram B, Becquet L, Wang Y, O'Dorisio MS, Waschek JA and Tan YV. Erratum to: VPAC1 receptor (Vipr1)-deficient mice exhibit ameliorated experimental autoimmune encephalomyelitis, with specific deficits in the effector stage. J Neuroinflammation 2017, 14: 157.
    28778207
  • Joly P, Maho-Vaillant M, Prost-Squarcioni C, Hebert V, Houivet E, Calbo S, Caillot F, Golinski ML, Labeille B, Picard-Dahan C, Paul C, Richard MA, Bouaziz JD, Duvert-Lehembre S, Bernard P, Caux F, Alexandre M, Ingen-Housz-Oro S, Vabres P, Delaporte E, Quereux G, Dupuy A, Debarbieux S, Avenel-Audran M, D'Incan M, Bedane C, Bénéton N, Jullien D, Dupin N, Misery L, Machet L, Beylot-Barry M, Dereure O, Sassolas B, Vermeulin T, Benichou J and Musette P; French study group on autoimmune bullous skin diseases. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet 2017, 389: 2031-2040.
    28342637

2015

  • Kipfer S, Frigerio S, Hench J, Aussy A and Boyer O. Immune-mediated necrotising myopathy linked to statin use. Lancet 2015
    26074381

2014

  • Bisson A, Corre SL, Joly-Helas G, Chambon P, Demoulins L, Jean L, Adriouch S, Drouot L, Giverne C, Roussel F, Jacquot S, Doucet C, Michot F, Lamacz M, Frebourg T, Flaman JM and Boyer O. Chromosomal instability but lack of transformation in human myoblast preparations. Cell Transplant 2014
    23866726
  • Bisson A, Fréret M, Drouot L, Jean L, Corre SL, Gourcerol G, Doucet C, Michot F, Boyer O and Lamacz M. Restoration of anal sphincter function after myoblast cell therapy in incontinent rats. Cell Transplant 2014
    24143883
  • Drouot L, Allenbach Y, Jouen F, Charuel JL, Martinet J, Meyer A, Hinschberger O, Bader-Meunier B, Kone-Paut I, Campana-Salort E, Eymard B, Tournadre A, Musset L, Sibilia J, Marie I, Benveniste O and Boyer O; French Myositis Network [CN]. Exploring necrotizing autoimmune myopathies with a novel immunoassay for anti-3-hydroxy-3-methyl-glutaryl-CoA reductase autoantibodies. Arthritis Res Ther 2014, 16: R39.
    24484965