Chronic enzyme replacement therapy ameliorates neuropathology in alpha-mannosidosis mice

Annals of Clinical and Translational Neurology
Markus DammeJudith Blanz

Abstract

The lysosomal storage disease alpha-mannosidosis is caused by the deficiency of the lysosomal acid hydrolase alpha-mannosidase (LAMAN) leading to lysosomal accumulation of neutral mannose-linked oligosaccharides throughout the body, including the brain. Clinical findings in alpha-mannosidosis include skeletal malformations, intellectual disabilities and hearing impairment. To date, no curative treatment is available. We previously developed a beneficial enzyme replacement therapy (ERT) regimen for alpha-mannosidase knockout mice, a valid mouse model for the human disease. However, humoral immune responses against the injected recombinant human alpha-mannosidase (rhLAMAN) precluded long-term studies and chronic treatment. Here, we describe the generation of an immune-tolerant alpha-mannosidosis mouse model that allowed chronic injection of rhLAMAN by transgenic expression of a catalytically inactive variant of human LAMAN in the knockout background. Chronic ERT of rhLAMAN revealed pronounced effects on primary substrate storage throughout the brain, normalization of lysosomal enzyme activities and morphology as well as a decrease in microglia activation. The positive effect of long-term ERT on neuronal lysosomal function was ref...Continue Reading

References

Sep 1, 1977·Journal of Neuropathology and Experimental Neurology·J H SungR J Desnick
Dec 1, 1987·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·S Kornfeld
Sep 1, 1969·The Journal of Pediatrics·B KjellmanB Palmgren
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·S U WalkleyS Wurzelmann
Jan 23, 1999·American Journal of Human Genetics·T BergO Nilssen
Feb 5, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·U DunderI Mononen
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·W S SlyE M Snella
Jul 7, 2001·The New England Journal of Medicine·C M EngUNKNOWN International Collaborative Fabry Disease Study Group
Mar 24, 2004·The Biochemical Journal·Gaute HansenOle K Tollersrud
Jul 23, 2004·Human Molecular Genetics·Diego Prieto RocesKurt von Figura
Aug 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Akihiko UrayamaWilliam A Banks
Jun 28, 2005·Molecular Genetics and Metabolism·Dongning WangAlessandra d'Azzo
Sep 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Carole VoglerWilliam S Sly
Jun 30, 2006·Molecular Genetics and Metabolism·Allison C CrawleyJohn J Hopwood
Jul 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Akihiko UrayamaWilliam S Sly
Oct 19, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shannon Reagan-ShawNihal Ahmad
Feb 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey H GrubbWilliam S Sly
Apr 30, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Akihiko UrayamaWilliam A Banks
Jun 14, 2008·Expert Opinion on Biological Therapy·Gregory M Pastores
Jul 25, 2008·Orphanet Journal of Rare Diseases·Dag Malm, Øivind Nilssen
Dec 3, 2008·Biochimica Et Biophysica Acta·Thomas Braulke, Juan S Bonifacino
Jan 29, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ulrich MatznerVolkmar Gieselmann
Dec 16, 2010·Journal of Neuropathology and Experimental Neurology·Markus DammeJudith Blanz
Apr 26, 2011·Experimental Neurology·Tina RozaklisKim M Hemsley
May 10, 2011·Bone Marrow Transplantation·M MynarekK-W Sykora
Sep 29, 2011·Current Opinion in Pediatrics·Robin H Lachmann
Oct 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ha T HuynhWilliam S Sly
Jun 7, 2013·Journal of Inherited Metabolic Disease·Dag MalmØivind Nilssen
Jun 22, 2013·Orphanet Journal of Rare Diseases·Michael BeckDag Malm
Oct 9, 2013·Molecular Genetics and Metabolism·Li OuChester B Whitley

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Citations

Jun 11, 2020·Cells·Brianna M NaumchikTroy C Lund
May 19, 2018·International Journal of Molecular Sciences·Maria Rachele CeccariniTommaso Beccari

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Methods Mentioned

BETA
electrophoresis
transgenic
ELISA
Light microscopy
enzyme replacement therapy
chemical modification
Genotyping

Software Mentioned

GraphPad Prism
GraphPad

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