Reversibility of motor dysfunction in the rat model of NGLY1 deficiency.

Molecular Brain
Makoto AsahinaTadashi Suzuki

Abstract

N-glycanase 1 (NGLY1) deficiency is a rare inherited disorder characterized by developmental delay, hypolacrima or alacrima, seizure, intellectual disability, motor deficits, and other neurological symptoms. The underlying mechanisms of the NGLY1 phenotype are poorly understood, and no effective therapy is currently available. Similar to human patients, the rat model of NGLY1 deficiency, Ngly1-/-, shows developmental delay, movement disorder, somatosensory impairment, scoliosis, and learning disability. Here we show that single intracerebroventricular administration of AAV9 expressing human NGLY1 cDNA (AAV9-hNGLY1) to Ngly1-/- rats during the weaning period restored NGLY1 expression in the brain and spinal cord, concomitant with increased enzymatic activity of NGLY1 in the brain. hNGLY1 protein expressed by AAV9 was found predominantly in mature neurons, but not in glial cells, of Ngly1-/- rats. Strikingly, intracerebroventricular administration of AAV9-hNGLY1 normalized the motor phenotypes of Ngly1-/- rats assessed by the rota-rod test and gait analysis. The reversibility of motor deficits in Ngly1-/- rats by central nervous system (CNS)-restricted gene delivery suggests that the CNS is the primary therapeutic target organs f...Continue Reading

References

Jun 1, 1995·Archives of Biochemistry and Biophysics·K KitajimaY Inoue
Jun 1, 2000·The Journal of Cell Biology·T SuzukiW J Lennarz
Sep 10, 2003·Molecular Biology of the Cell·Stephan Seiler, Michael Plamann
Apr 18, 2008·Gene Therapy·C Mueller, T R Flotte
Aug 7, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Douglas M McCarty
Feb 5, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Nasrin Habibi-BabadiAntonio Colavita
May 15, 2012·Journal of Medical Genetics·Anna C NeedDavid B Goldstein
Mar 22, 2014·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Gregory M EnnsDavid B Goldstein
Sep 16, 2014·European Journal of Medical Genetics·Ahmet Okay CaglayanMurat Gunel
Jan 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Chengcheng HuangTadashi Suzuki
Feb 25, 2015·American Journal of Medical Genetics. Part a·Jennifer Heeley, Marwan Shinawi
Sep 10, 2015·European Journal of Human Genetics : EJHG·Daniëlle G M BoschBert B A de Vries
Dec 15, 2015·Biochimica Et Biophysica Acta·Milos Pekny, Marcela Pekna
Jul 9, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Christina LamLynne Wolfe
Aug 23, 2017·ELife·Antonio GaleoneHamed Jafar-Nejad
May 8, 2018·G3 : Genes - Genomes - Genetics·Tamy Portillo RodriguezEthan O Perlstein
Aug 24, 2018·The Journal of Experimental Medicine·Kun YangNan Yan
Jun 21, 2019·Orphanet Journal of Rare Diseases·Eli M Cahan, Steven L Frick
Jul 18, 2019·Molecular Genetics and Metabolism·Hanneke A HaijesJudith J M Jans
Nov 17, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Haruhiko FujihiraTadashi Suzuki
May 19, 2020·European Journal of Medical Genetics·Izabel Maryalexandra Rios-FloresJorge Román Corona-Rivera
May 21, 2020·Polish Journal of Pathology : Official Journal of the Polish Society of Pathologists·Patryk LipińskiAnna Tylki-Szymańska
Jul 29, 2020·ELife·Antonio GaleoneHamed Jafar-Nejad
Dec 15, 2020·ELife·Dana M TalsnessClement Y Chow
Dec 15, 2020·PLoS Genetics·Seung Yeop HanHamed Jafar-Nejad
Jan 27, 2021·European Journal of Medical Genetics·Ariana KariminejadRaoul C Hennekam
Feb 11, 2021·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Makoto AsahinaTadashi Suzuki

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Citations

Aug 18, 2021·Molecular Brain·Makoto AsahinaTadashi Suzuki
Sep 29, 2021·Journal of Biochemistry·Haruhiko FujihiraTadashi Suzuki
Oct 27, 2021·Journal of Biochemistry·William F MuellerBrett E Crawford

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