Long-term neurologic and cardiac correction by intrathecal gene therapy in Pompe disease
2017
Hordeaux, Juliette | Dubreil, Laurence | Robeveille, Cynthia | Deniaud, Johan | Pascal, Quentin | Dequeant, Bérangère | Pailloux, Julie | Lagalice, Lydie | Ledevin, Mireille | Babarit, Candice | Costiou, Patrick | Jamme, Frederic | Fusellier, M. | Mallem, Yassine | Ciron, Carine | Huchet, Corinne | Caillaud, Catherine | Colle, Marie-Anne | Institut National de la Recherche Agronomique (INRA) | Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher) ; École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | LUNAM Université [Nantes Angers Le Mans] | Département Caractérisation et Elaboration des Produits Issus de l'Agriculture (CEPIA) ; Institut National de la Recherche Agronomique (INRA) | Synchrotron SOLEIL (SSOLEIL) ; Centre National de la Recherche Scientifique (CNRS) | 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) | Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)) ; Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | Region Pays de la Loire; National French Academy of Medicine and "Investissement d'Avenir" - - "NeurATRIS: A Translational Research Infrastructure for Biotherapies in Neurosciences" (MAC) [ANR-11-INBS-0011]; French Government | ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011)
International audience
اظهر المزيد [+] اقل [-]إنجليزي. Pompe disease is a lysosomal storage disorder caused by acid-a-glucosidase (GAA) deficiency, leading to glycogen storage. The disease manifests as a fatal cardiomyopathy in infantile form. Enzyme replacement therapy (ERT) has recently prolonged the lifespan of these patients, revealing a new natural history. The neurologic phenotype and the persistence of selective muscular weakness in some patients could be attributed to the central nervous system (CNS) storage uncorrected by ERT. GAA-KO 6neo/6neo mice were treated with a single intrathecal administration of adeno-associated recombinant vector (AAV) mediated gene transfer of human GAA at 1 month and their neurologic, neuromuscular, and cardiac function was assessed for 1 year. We demonstrate a significant functional neurologic correction in treated animals from 4 months onward, a neuromuscular improvement from 9 months onward, and a correction of the hypertrophic cardiomyopathy at 12 months. The regions most affected by the disease i.e. the brainstem, spinal cord, and the left cardiac ventricular wall all show enzymatic, biochemical and histological correction. Muscle glycogen storage is not affected by the treatment, thus suggesting that the restoration of muscle functionality is directly related to the CNS correction. This unprecedented global and long-term CNS and cardiac cure offer new perspectives for the management of patients.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل Institut national de la recherche agronomique
