Long-term Improvements in Lifespan and Pathology in CNS and PNS After BMT Plus One Intravenous Injection of AAVrh10-GALC in Twitcher Mice

Molecular Therapy : the Journal of the American Society of Gene Therapy
M A RafiD A Wenger

Abstract

Krabbe disease is an autosomal recessive disorder resulting from defects in the lysosomal enzyme galactocerebrosidase (GALC). GALC deficiency leads to severe neurological features. The only treatment for presymptomatic infantile patients and later-onset patients is hematopoietic stem cell transplantation (HSCT). This treatment is less than ideal with most patients eventually developing problems with gait and expressive language. Several naturally occurring animal models are available, including twitcher (twi) mice, which have been used for many treatment trials. Previous studies demonstrated that multiple injections of AAVrh10-GALC into the central nervous system (CNS) of neonatal twi mice resulted in significant improvements. Recently we showed that one i.v. injection of AAVrh10-GALC on PND10 resulted in normal GALC activity in the CNS and high activity in the peripheral nervous system (PNS). In the present study, a single i.v. injection of AAVrh10-GALC was given 1 day after bone marrow transplantation (BMT) on PND10. The mice show greatly extended lifespan and normal behavior with improved CNS and PNS findings. Since HSCT is the standard of care in human patients, adding this single i.v. injection of viral vector may greatly ...Continue Reading

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Citations

Aug 16, 2016·BioImpacts : BI·Mohammad A Rafi
Sep 18, 2016·Journal of Neuroscience Research·David A WengerPaola Luzi
Sep 18, 2016·Journal of Neuroscience Research·Joseph J OrsiniMichele Caggana
Sep 18, 2016·Journal of Neuroscience Research·Keri R Maher, Andrew M Yeager
Sep 18, 2016·Journal of Neuroscience Research·Glyn Dawson
Sep 18, 2016·Journal of Neuroscience Research·Subha Karumuthil-Melethil, Steven J Gray
May 1, 2020·Frontiers in Molecular Biosciences·Jacob M FavretDaesung Shin
Jul 21, 2020·JIMD Reports·David A Wenger, Paola Luzi
Sep 18, 2016·Journal of Neuroscience Research·Je-Seong WonInderjit Singh
Sep 18, 2016·Journal of Neuroscience Research·Gregory B Potter, Magdalena A Petryniak
Aug 26, 2016·Journal of Neuroscience Research·Yoichi Kondo, Ian D Duncan
Apr 27, 2017·Scientific Reports·Valentina CappelloMauro Gemmi
Sep 18, 2016·Journal of Neuroscience Research·Christina R Mikulka, Mark S Sands
Sep 18, 2016·Journal of Neuroscience Research·Alice LuddiElvira Costantino-Ceccarini
Jan 4, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yedda LiMark S Sands
Jan 29, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Gregory J HellerErnesto R Bongarzone
Mar 4, 2021·Expert Opinion on Biological Therapy·Azam SafaryYadollah Omidi
Apr 24, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Aaron Mitchell-Dick, Aravind Asokan
Aug 28, 2021·International Journal of Neonatal Screening·David A WengerMohammad A Rafi

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