Publications

Dernière publication 08/01/2018

Intravenous administration of scAAV9-Hexb normalizes lifespan and prevents patho

Sandhoff disease (SD) is a rare inherited disorder caused by a deficiency of β-hexosaminidase activity which is fatal because no effective...

Array
(
    [id_prestablog_news] => 927
    [id_shop] => 1
    [date] => 2018-01-08 00:00:00
    [date_modification] => 2024-02-09 14:15:12
    [langues] => ["1","2"]
    [actif] => 1
    [slide] => 0
    [url_redirect] => 
    [average_rating] => 
    [number_rating] => 
    [author_id] => 1
    [featured] => 0
    [prim_key] => 1818
    [id_lang] => 2
    [title] => Intravenous administration of scAAV9-Hexb normalizes lifespan and prevents patho
    [paragraph] => Intravenous administration of scAAV9-Hexb normalizes lifespan and prevents pathology in Sandhoff disease mice
    [content] => 
Authors
N. Niemer, L. Rouviere, A. Besse, M.T. Vanier, J. Dmytrus, T. Marais, S. Astord, J-P. Puech, G. Panasyuk, J.D. Cooper, M. Barkats, C. Caillaud

 Lab
Institut Necker-Enfants Malades, Paris, France
Journal
Human Molecular Genetics
Abstract
Sandhoff disease (SD) is a rare inherited disorder caused by a deficiency of β-hexosaminidase activity which is fatal because no effective treatment is available. A mouse model of Hexb deficiency reproduces the key pathognomonic features of SD patients with severe ubiquitous lysosomal dysfunction, GM2 accumulation, neuroinflammation and neurodegeneration, culminating in death at 4 months. Here, we show that a single intravenous neonatal administration of a self-complementary adeno-associated virus 9 vector (scAAV9) expressing the Hexb cDNA in SD mice is safe and sufficient to prevent disease development. Importantly, we demonstrate for the first time that this treatment results in a normal lifespan (over 700 days) and normalizes motor function assessed by a battery of behavioral tests, with scAAV9-treated SD mice being indistinguishable from wild-type littermates. Biochemical analyses in multiple tissues showed a significant increase in hexosaminidase A activity, which reached 10-15% of normal levels. AAV9 treatment was sufficient to prevent GM2 and GA2 storage almost completely in cerebrum (less so in cerebellum), as well as thalamic reactive gliosis and thalamocortical neuron loss in treated Hexb-/- mice. In summary, this study demonstrated a widespread protective effect throughout the entire CNS after a single intravenous administration of scAAV9-Hexb vector to neonatal SD mice.
BIOSEB Instruments Used
Aron Test or Four Plates Test (LE830),Activmeter (BIO-ACTIV-R),Rotarod (BX-ROD)
    [meta_description] => 
    [meta_keywords] => https://academic.oup.com/hmg/advance-article-abstract/doi/10.1093/hmg/ddy012/4793002?redirectedFrom=fulltext
    [meta_title] => 
    [link_rewrite] => intravenous-administration-of-scaav9-hexb-normalizes-lifespan-and-prevents-pathology-in-sandhoff-disease-mice
    [actif_langue] => 1
    [read] => 1057
    [count_comments] => 0
    [id] => 927
    [categories] => Array
        (
            [96] => Array
                (
                    [id_prestablog_categorie] => 96
                    [title] => Autres pathologies
                    [link_rewrite] => Autres-pathologies
                )

            [2] => Array
                (
                    [id_prestablog_categorie] => 2
                    [title] => Publications
                    [link_rewrite] => publications
                )

            [25] => Array
                (
                    [id_prestablog_categorie] => 25
                    [title] => Thematiques diverses
                    [link_rewrite] => Thematiques-diverses
                )

        )

    [authors] => 
    [paragraph_crop] => Intravenous administration of scAAV9-Hexb normalizes lifespan and prevents pathology in [...]
    [link_for_unique] => 1
    [products_liaison] => Array
        (
            [588] => Array
                (
                    [name] => Test d'Aron ou 'Four Plates Test'
                    [description_short] => 
Le 'Four Plates Test' ou test d'Aron est une exclusivité Bioseb!
Un outil rapide pour l'évaluation de substances anxiolytiques putatives chez l'animal naïf. Un "must" pour l'étude de l'anxiété, le screening des drogues et le phénotypage.
                    [thumb] => 
                    [img_empty] => /var/www/vhosts/de3310.ispfr.net/preprod.bioseb.com/modules/prestablog/views/img/product_link_white.jpg
                    [image_presente] => 1
                    [link] => https://preprod.bioseb.com/fr/anxiete-depression/588-aron-test-or-four-plates-test.html
                )

            [898] => Array
                (
                    [name] => Activmètre
                    [description_short] => 
Une façon simple pour mesurer l'activité des rongeurs sur plusieurs jours dans leurs cages de vie. Basé uniquement sur l'analyse du poids de l'animal, L'ACTIVMETRE Bioseb permet une mesure précise de l'activité et des déplacements du rongeur (rat et souris), dans toutes les conditions d'éclairage.
fiber_new Possibilité d’ajouter la mesure de l’activité verticale des animaux dans la cage (en option).

                    [thumb] => 
                    [img_empty] => /var/www/vhosts/de3310.ispfr.net/preprod.bioseb.com/modules/prestablog/views/img/product_link_white.jpg
                    [image_presente] => 1
                    [link] => https://preprod.bioseb.com/fr/activite-systeme-moteur-coordination/898-activmeter.html
                )

            [1326] => Array
                (
                    [name] => Rotarod pour rats et souris
                    [description_short] => 
Le Rotarod offre une méthode facile pour le test de l'activité motrice chez les rongeurs (rats ou souris) - une solution idéale pour étudier les lésions du système nerveux central (SNC), les effets de différentes pathologies et substances pharmacologiques sur l'activité motrice, la résistance à la fatigue, etc. Désormais encore plus simple d'utilisation! La nouvelle interface utilisateur graphique et tactile permet une visualisation claire de la vitesse et des temps associés à chaque piste. Vous pouvez maintenant changer de mode, régler la vitesse et créer des protocoles directement depuis l'écran principal for une une plus grande flexibilité et un maximum de fonctionnalités.

                    [thumb] => 
                    [img_empty] => /var/www/vhosts/de3310.ispfr.net/preprod.bioseb.com/modules/prestablog/views/img/product_link_white.jpg
                    [image_presente] => 1
                    [link] => https://preprod.bioseb.com/fr/activite-systeme-moteur-coordination/1326-rotarod.html
                )

        )

)
1