📇 Rhumatologue · LE MANS CEDEX 2 · (72) · Mixte

M Benoit GAUTIER

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Praticien-chercheur
13 articles scientifiques publiés — formation continue solide
Cabinet de groupe — continuité de soins
Plusieurs praticiens dans le même cabinet — un confrère peut prendre le relais en cas d'absence
Expérience confirmée
17 ans d'exercice en rhumatologie — recul clinique solide
Disponibilité géographique
9 lieux d'exercice — choisissez celui qui vous arrange
Délais de RDV courts dans la région
77.4 rhumatos / 100 000 hab. — département bien doté

Rhumatologue

📍 LE MANS CEDEX 2 (72)MixteRPPS 10002075215

Expérience confirmée

17ans d'exercice (thèse 2009)

📊 Reconnaissance scientifique : 23/100📝 51 articles publiés🇫🇷 Publications académiques françaises (8)

✨ Génération du profil synthétique IA en cours…

Thèses universitaires

Données ANS publiques (Licence Ouverte 2.0) · Enrichissements MonRhumato 100 % opt-in · Toute personne référencée peut demander la suppression ou la rectification.

Top publications · les plus citées

Intracerebral Gene Therapy Using AAVrh.10-hARSA Recombinant Vector to Treat Patients with Early-Onset Forms of Metachromatic Leukodystrophy: Preclinical Feasibility and Safety Assessments in Nonhuman Primates

Human gene therapy. Clinical development · 2015

📚 74 citations🎯 RCR 2.47Top 21% NIH🩺 Clinique

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No treatment is available for early-onset forms of metachromatic leukodystrophy (MLD), a lysosomal storage disease caused by autosomal recessive defect in arylsulfatase A ( ARSA ) gene causing severe demyelination in central and peripheral nervous systems. We have developed a gene therapy approach, based on intracerebral administration of AAVrh.10-hARSA vector, coding for human ARSA enzyme. We have previously demonstrated potency of this approach in MLD mice lacking ARSA expression. We describe herein the preclinical efficacy, safety, and biodistribution profile of intracerebral administration of AAVrh.10-hARSA to nonhuman primates (NHPs). NHPs received either the dose planned for patients adjusted to the brain volume ratio between child and NHP (1×dose, 1.1×10 11 vg/hemisphere, unilateral or bilateral injection) or 5-fold this dose (5×dose, 5.5×10 11 vg/hemisphere, bilateral injection). NHPs were subjected to clinical, biological, and brain imaging observations and were euthanized 7 or 90 days after injection. There was no toxicity based on clinical and biological parameters, nor treatment-related histological findings in peripheral organs. A neuroinflammatory process correlating with brain MRI T2 hypersignals was observed in the brain 90 days after administration of the 5×dose, but was absent or minimal after administration of the 1×dose. Antibody response to AAVrh.10 and hARSA was detected, without correlation with brain lesions. After injection of the 1×dose, AAVrh.10-hARSA vector was detected in a large part of the injected hemisphere, while ARSA activity exceeded the normal endogenous activity level by 14–31%. Consistently with other reports, vector genome was detected in off-target organs such as liver, spleen, lymph nodes, or blood, but not in gonads. Importantly, AAVrh.10-hARSA vector was no longer detectable in urine at day 7. Our data demonstrate requisite safe and effective profile for intracerebral AAVrh.10-hARSA delivery in NHPs, supporting its clinical use in children affected with MLD.

AAV2/9-mediated silencing of PMP22 prevents the development of pathological features in a rat model of Charcot-Marie-Tooth disease 1 A

Nature communications · 2021

📚 58 citations🎯 RCR 4.31Top 10% NIH🔓 Open Access📄 PDF gratuit ↗

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AbstractCharcot-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.

Diffusion-weighted Imaging Is a Sensitive and Specific Magnetic Resonance Sequence in the Diagnosis of Ankylosing Spondylitis

The Journal of rheumatology · 2018

📚 38 citations🎯 RCR 2.41Top 21% NIH

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Objective. We tested the discriminatory capacity of diffusion-weighted magnetic resonance imaging (DWI) and its potential as an objective measure of treatment response to tumor necrosis factor inhibition in ankylosing spondylitis (AS). Methods. Three cohorts were studied prospectively: (1) 18 AS patients with Bath Ankylosing Spondylitis Disease Activity Index > 4, and erythrocyte sedimentation rate > 25 and/or C-reactive protein > 10 meeting the modified New York criteria for AS; (2) 20 cases of nonradiographic axial spondyloarthritis (nr-axSpA) as defined by the Assessment of Spondyloarthritis international Society (ASAS) criteria; and (3) 20 non-AS patients with chronic low back pain, aged between 18 and 45 years, who did not meet the imaging arm of the ASAS criteria for axSpA. Group 1 patients were studied prior to and following adalimumab treatment. Patients were assessed by DWI and conventional magnetic resonance imaging (MRI), and standard nonimaging measures. Results. At baseline, in contrast to standard nonimaging measures, DWI apparent diffusion coefficient (ADC) values showed good discriminatory performance [area under the curve (AUC) > 80% for Group 1 or 2 compared with Group 3]. DWI ADC values were significantly lower posttreatment (0.45 ± 0.433 before, 0.154 ± 0.23 after, p = 0.0017), but had modest discriminating capacity comparing pre– and posttreatment measures (AUC = 68%). This performance was similar to the manual Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. Conclusion. DWI is informative for diagnosis of AS and nr-axSpA, and has moderate utility in assessment of disease activity or treatment response, with performance similar to that of the SPARCC MRI score.

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M Benoit GAUTIER

Pourquoi vous devez consulter ce praticien

Thèses universitaires

Activité de recherche & publications

Publications académiques en France

Lieux de consultation(9)

Tarifs & secteur de conventionnement

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Top publications · les plus citées

Publications scientifiques (13) — classées par pathologie

Transversal8

Biomarqueurs / Auto-Ac1

Goutte1

IRM ostéo-articulaire1

Pharmacovigilance1

Risque cardio-vasculaire1

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