A5058481477- Lysosomal Storage Disorders Research
- Virus-based gene therapy research
- Neurological diseases and metabolism
- Alzheimer's disease research and treatments
- Retinal Development and Disorders
- RNA regulation and disease
- Autophagy in Disease and Therapy
- Glycogen Storage Diseases and Myoclonus
- Herpesvirus Infections and Treatments
- Neurogenetic and Muscular Disorders Research
- Hereditary Neurological Disorders
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Dementia and Cognitive Impairment Research
- Trypanosoma species research and implications
- Prion Diseases and Protein Misfolding
- Biotin and Related Studies
- Cytomegalovirus and herpesvirus research
- Mitochondrial Function and Pathology
- Genetic Neurodegenerative Diseases
- Advanced Biosensing Techniques and Applications
- Muscle Physiology and Disorders
- Metabolism and Genetic Disorders
- bioluminescence and chemiluminescence research
- Retinopathy of Prematurity Studies
Oniris
2014-2024
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2009-2024
Nerve Centre
2012-2023
PAnTher - Physiopathologie Animale et bioThérapie du muscle et du système nerveux
2012-2023
Université Bretagne Loire
2017-2018
Institut National de la Recherche Agronomique
2012
École Normale Supérieure - PSL
2010
École Nationale Vétérinaire de Toulouse
2009
École Pratique des Hautes Études
2001
Pitié-Salpêtrière Hospital
1998
The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand correlates protection against and disease in order inform development new interventions. Herein we highlight propensity CHIKV infections persist long term, both as persistent, steady-state, viraemias multiple B cell deficient mouse strains, persistent RNA (including negative-strand RNA) wild-type mice. knockout studies provided evidence for role T cells (but not NK cells)...
Recent trials in patients with neurodegenerative diseases documented the safety of gene therapy based on adeno-associated virus (AAV) vectors deposited into brain. Inborn errors metabolism are most frequent causes neurodegeneration pre-adulthood. In Sanfilippo syndrome, a lysosomal storage disease which heparan sulfate oligosaccharides accumulate, onset clinical manifestation is before 5 years. Studies mouse model showed that providing missing enzyme α-N-acetyl-glucosaminidase to brain cells...
The identification of the most efficient method for whole central nervous system targeting that is translatable to humans and safest route adeno-associated virus (AAV) administration a major concern future applications in clinics. Additionally, as many AAV serotypes were identified gene introduction into brain spinal cord, another key human gene-therapy success determine serotype. In this study, we compared lumbar intrathecal through catheter implantation intracerebroventricular cynomolgus...
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 central and peripheral nervous systems. We have developed therapy approach, based on intracerebral administration AAVrh.10-hARSA vector, coding human ARSA enzyme. previously demonstrated potency this approach MLD mice lacking expression. describe herein the preclinical efficacy,...
A defect of the lysosomal enzyme alpha-L-iduronidase (IDUA) interrupts degradation glycosaminoglycans in mucopolysaccharidosis type I, causing severe neurological manifestations children with Hurler's syndrome. Delivery missing through stereotactic injection adeno-associated virus vectors coding for IDUA prevents neuropathology affected mice. We examined efficacy and safety this approach enzyme-deficient dogs.Because deficient dogs raise antibodies against response to infusion, intracerebral...
Recombinant adeno-associated virus (rAAV) vectors are among the most efficient gene delivery vehicles for transfer to retina. This study evaluates behavior of rAAV8 serotype vector with regard intraocular in rats and dogs. Subretinal an AAV2/8.gfp results retinal pigment epithelium (RPE), photoreceptors and, surprisingly, cells inner nuclear layer as well ganglion cells. Most importantly, dogs, also occurred distal injection site neurons lateral geniculate nucleus brain. Because green...
For the development of new therapies, proof-of-concept studies in large animal models that share clinical features with their human counterparts represent a pivotal step. inherited retinal dystrophies primarily involving photoreceptor cells, efficacy gene therapy has been demonstrated canine stationary cone and progressive rod–cone but not cone–rod dystrophies, another important cause blindness. To address last issue, we evaluated retinitis pigmentosa GTPase regulator interacting protein 1...
Defects in the β subunit of rod cGMP phosphodiesterase 6 (PDE6β) are associated with autosomal recessive retinitis pigmentosa (RP), a childhood blinding disease early retinal degeneration and vision loss. To date, there is no treatment for this pathology. The aim preclinical study was to test recombinant adeno-associated virus (AAV)-mediated gene addition therapy rod-cone dysplasia type 1 (rcd1) dog, large animal model naturally occurring PDE6β deficiency that strongly resembles human A...
In order to assess the therapeutic potential of cell-based strategies, it is paramount importance elaborate and validate tools for monitoring behavior injected cells in terms tissue dissemination engraftment properties. Here, we apply bismuth ferrite harmonic nanoparticles (BFO HNPs) vitro expanded human skeletal muscle-derived stem (hMuStem cells), an attractive avenue patients suffering from Duchenne muscular dystrophy (DMD). We demonstrate possibility cell labeling with HNPs. also show...
The purpose of our study was to evaluate the biodistribution rAAV vectors following subretinal or intravitreal injection. In rats, we performed injections rAAV-2/2.CMV.gfp. large animals, rAAV-2/4.CMV.gfp rAAV-2/5.CMV.gfp delivered into space while rAAV-2/2.CMV.gfp either vitreous. euthanized undertook a complete necropsy. animals maintained alive, collected blood and tissue samples from submandibular lymph node, liver, gonads. We analyzed total DNA, extracted various peripheral mononuclear...
We have previously demonstrated that delivery of a recombinant adeno-associated virus (rAAV) encoding human alpha-iduronidase (hIDUA) in the putamen and centrum semiovale was feasible beneficial dog model Hurler's syndrome. In present study, we investigated safety vector diffusion profile three rAAV serotypes (rAAV2/1, rAAV2/2, rAAV2/5), hIDUA central peripheral nervous systems nonhuman primates. Six macaques received same dose injected into right homolateral internal capsule. Neurological...
We previously reported that subretinal injection of AAV2/5 RK.cpde6β allowed long-term preservation photoreceptor function and vision in the rod-cone dysplasia type 1 (rcd1) dog, a large animal model naturally occurring PDE6β deficiency. The present study builds on these earlier findings to provide detailed assessment effects gene therapy spatiotemporal pattern retinal degeneration rcd1 dogs treated at 20 days age. analyzed density distribution layers particular cells 3.5-year-old untreated...
Recombinant adeno-associated virus (AAV) has emerged as a promising vector for retinal gene delivery to restore visual function in certain forms of inherited dystrophies. Several studies rodent models have shown that intravitreal injection the AAV2/2 is optimal route efficient ganglion cell (RGC) transduction. However, translation these findings larger species, including humans, complicated by anatomical differences eye, key difference being comparatively smaller volume vitreous chamber...
Thirteen dogs, including 6 Rottweiler exhibiting clinical signs of spinal cord dysfunction and myelographically confirmed subarachnoid space enlargement were investigated. To characterize the lesions to get a better understanding their pathogenesis, different imaging techniques used in association with explorative surgical procedures (12 dogs) histopathologic (5 dogs). All subjects underwent preoperative myelography, five which examined by computed tomography (CT) scanning one magnetic...
Pompe disease, which is due to acid alpha-glucosidase deficiency, characterized by skeletal muscle dysfunction attributed the accumulation of glycogen-filled lysosomes and autophagic buildup. Despite extensive tissue damages, a failure satellite cell (SC) activation lack regeneration have been reported in patients. However, origin this defective program unknown. Additionally, whether these deficits occur gradually over disease course unclear. Using longitudinal pathophysiological study two...
Severe deficiency in lysosomal β-glucuronidase (β-glu) enzymatic activity results mucopolysaccharidosis (MPS) VII, an orphan disease with symptoms often appearing early childhood. Symptoms are variable, but many patients have multiple organ disorders including neurological defects. At the cellular level, β-glu leads to abnormal accumulation of glycosaminoglycans (GAGs), and secondary GM2 GM3 gangliosides, which been linked neuroinflammation. There encouraging gene transfer studies MPS VII...
NEUROFIBRILLARY tangles and neuropil threads, both made of hyperphosphorylated tau proteins, point to an alteration microtubules in Alzheimer's disease. The aim this study was test the consequences these lesions on axoplasmic flow, which is dependent intact microtubule assembly. We assessed transport synaptic proteins from neuronal cell body axonal terminals, using SNAP-25 (synaptosomal-associated protein 25 kD) immunohistochemistry as a marker impaired transport. A sample supramarginalis...
Rift Valley fever (RVF) is one of the major viral arthropod-borne diseases in Africa. In recent decades, RVF virus (RVFV), causative agent RVF, has been responsible for multiple outbreaks West Africa with important consequences on human and animal health. particular, an outbreak occurred 2010 after heavy rains desertic region Adrar, Mauritania. It was characterized by appearance severe clinical signs among dromedary camels. Another 2013–2014 across Senegal southern part this study, we two...
Summary We report a case of systemic xanthomatosis in 4‐month‐old domestic cat. The kitten presented with multiple cutaneous lesions and ‘cream tomato soup’ coloured blood. Necropsy revealed multiple, whitish, nodular lesions, compatible xanthomas, on most the abdominal organs (liver, spleen, kidney, adrenal glands, mesentery colon). diagnosis was confirmed by histopathological examination. This is first granulomatous colitis associated feline xanthomatosis.