3 results on '"Cyril Rivat"'
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2. Inhibition of neuronal FLT3 receptor tyrosine kinase alleviates peripheral neuropathic pain in mice
- Author
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Cyril Rivat, Chamroeun Sar, Ilana Mechaly, Jean-Philippe Leyris, Lucie Diouloufet, Corinne Sonrier, Yann Philipson, Olivier Lucas, Sylvie Mallié, Antoine Jouvenel, Adrien Tassou, Henri Haton, Stéphanie Venteo, Jean-Philippe Pin, Eric Trinquet, Fabienne Charrier-Savournin, Alexandre Mezghrani, Willy Joly, Julie Mion, Martine Schmitt, Alexandre Pattyn, Frédéric Marmigère, Pierre Sokoloff, Patrick Carroll, Didier Rognan, and Jean Valmier
- Subjects
Science - Abstract
Sensitisation of dorsal root ganglia neurons contributes to neuropathic pain. Here the authors demonstrate the cytokine FL contributes to sensitisation of DRGs via its receptor FLT3 expressed on neurons, and identify a novel FLT3 inhibitor that attenuates neuropathic pain in mice.
- Published
- 2018
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3. AAV2/9-mediated silencing of PMP22 prevents the development of pathological features in a rat model of Charcot-Marie-Tooth disease 1 A
- Author
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Graham Campbell, Sylvia Soares, Cyril Rivat, Nicolas Tricaud, Robert Fledrich, Sergio González, Marie Deck, Vlad Schütza, Caroline Le Guiner, Maria Ceprian, Jade Berthelot, Antoine Jouvenel, Scarlette Abbou, Benoit Gautier, Virginie François, Helene Hajjar, Claire-Maëlle Fovet, Patrick Aubourg, M. Zerah, Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), LPHI - Laboratory of Pathogen Host Interactions (LPHI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Leipzig University, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques (Inserm UMR 1089), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Unité de rééducation neurologique pédiatrique [Bicêtre], Hôpital Bicêtre, Thérapie génique, Génomique et Epigénomique (U 1169), Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Gestionnaire, Hal Sorbonne Université, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Laboratory of Pathogen Host Interactions [Montpellier] (LPHI)
- Subjects
0301 basic medicine ,Male ,Pathology ,Foot drop ,[SDV]Life Sciences [q-bio] ,Myelin biology and repair ,General Physics and Astronomy ,Nerve conduction velocity ,Mice ,0302 clinical medicine ,Charcot-Marie-Tooth Disease ,Gene duplication ,RNA, Small Interfering ,Multidisciplinary ,Developmental disorders ,Dependovirus ,Sciatic Nerve ,3. Good health ,[SDV] Life Sciences [q-bio] ,Female ,Sciatic nerve ,medicine.symptom ,Myelin Proteins ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,Transgene ,Science ,Genetic Vectors ,General Biochemistry, Genetics and Molecular Biology ,Article ,Rats, Mutant Strains ,Viral vector ,03 medical and health sciences ,Immune system ,medicine ,Gene silencing ,Animals ,Humans ,Gene Silencing ,business.industry ,General Chemistry ,Genetic Therapy ,Rats ,Mice, Inbred C57BL ,Disease Models, Animal ,Macaca fascicularis ,030104 developmental biology ,Schwann Cells ,business ,Somatic system ,030217 neurology & neurosurgery - Abstract
Charcot-Marie-Tooth disease 1 A (CMT1A) results from a duplication of the PMP22 gene in Schwann cells and a deficit of myelination in peripheral nerves. Patients with CMT1A have reduced nerve conduction velocity, muscle wasting, hand and foot deformations and foot drop walking. Here, we evaluate the safety and efficacy of recombinant adeno-associated viral vector serotype 9 (AAV2/9) expressing GFP and shRNAs targeting Pmp22 mRNA in animal models of Charcot-Marie-Tooth disease 1 A. Intra-nerve delivery of AAV2/9 in the sciatic nerve allowed widespread transgene expression in resident myelinating Schwann cells in mice, rats and non-human primates. A bilateral treatment restore expression levels of PMP22 comparable to wild-type conditions, resulting in increased myelination and prevention of motor and sensory impairments over a twelve-months period in a rat model of CMT1A. We observed limited off-target transduction and immune response using the intra-nerve delivery route. A combination of previously characterized human skin biomarkers is able to discriminate between treated and untreated animals, indicating their potential use as part of outcome measures., Charcot-Marie-Tooth disease 1 A (CMT1A) results from PMP22 gene duplication and is characterized by peripheral nerve myelination deficits. Here, the authors prevent the development of pathological features in a rat model of CMT1A through the local delivery of AAV2/9 expressing shRNAs against PMP22.
- Published
- 2021
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