Genetic correction of the fetal brain increases the lifespan of mice with the severe multisystemic disease mucopolysaccharidosis type VII

Molecular Therapy : the Journal of the American Society of Gene Therapy
Brian A Karolewski, John H Wolfe

Abstract

Neurogenetic diseases typically have globally distributed lesions, and pathology usually develops early in life, requiring early diagnosis and treatment. We investigated the effects of transferring a corrective gene into the fetal brain before the onset of pathology in the mucopolysaccharidosis (MPS) type VII mouse, a model of a lysosomal storage disease. A single adeno-associated virus serotype 1 vector injection into the ventricle at 15.5 days of gestation resulted in widespread distribution and lifelong expression of the normal gene in the brain and spinal cord. The normal enzyme was distributed to neighboring cells (as expected) and completely prevented the development of storage lesions throughout the central nervous system (CNS). No vector transfer was found outside the CNS, including the gonads, but a small amount of enzyme was present in visceral tissues, consistent with transfer from cerebrospinal fluid to venous circulation. The enzyme was present peripherally in such low amounts that it did not result in the severe skeletal dysmorphology that occurs readily when systemic treatment is used in neonates. However, the survival probability of the treated animals was significantly increased. The results suggest that the ne...Continue Reading

References

Jun 1, 1994·The Journal of Clinical Investigation·M S SandsE H Birkenmeier
Jan 26, 1999·JAMA : the Journal of the American Medical Association·P J MeikleW F Carey
Jun 1, 2000·Pediatric Research·M L Casal, J H Wolfe
Mar 29, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·G S LipshutzK M Gaensler
Feb 21, 2002·Vision Research·B ChangJ R Heckenlively
Sep 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Katherine Parker PonderMark E Haskins
Sep 23, 2003·Gene Therapy·Charles H ViteJohn H Wolfe
Dec 11, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Hee-Kyung Jin, Edward H Schuchman
May 11, 2004·The Journal of Gene Medicine·N Matthew EllinwoodMark E Haskins
Sep 7, 2004·Expert Review of Molecular Diagnostics·Peter J MeikleJohn J Hopwood
Apr 27, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mohammad A RafiDavid A Wenger
Apr 27, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Marco A PassiniGregory R Stewart
Aug 10, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tonia LucaErnesto R Bongarzone
Jan 18, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Cassia N Cearley, John H Wolfe

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Citations

Apr 1, 2011·Therapeutic Delivery·Suzanne M K BuckleySimon N Waddingtont
Apr 1, 2011·Therapeutic Delivery·Ahad A RahimSimon N Waddington
Jul 7, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Su XuPeter Lobel
Jul 3, 2007·Pharmaceutical Research·Yun ZhangWilliam M Pardridge
Feb 6, 2010·Expert Opinion on Biological Therapy·Brooke R SnyderThais Federici
Jun 1, 2011·Expert Opinion on Biological Therapy·Citra N MattarJerry K Y Chan
Jan 24, 2014·Expert Opinion on Drug Delivery·Guilherme BaldoUrsula Matte
Dec 17, 2014·Expert Opinion on Drug Delivery·Daniel A WolfWalter C Low
Aug 31, 2007·Expert Opinion on Biological Therapy·Katherine P Ponder, Mark E Haskins
Sep 12, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sea Young YoonJohn H Wolfe
Jul 24, 2012·Best Practice & Research. Clinical Obstetrics & Gynaecology·Citra N MattarAmit C Nathwani
Jun 23, 2009·Seminars in Fetal & Neonatal Medicine·Jessica L RoybalAlan W Flake
Jun 30, 2009·Clinics in Perinatology·Matthew T SantoreAlan W Flake
Aug 8, 2007·Molecular Genetics and Metabolism·Ainslie L K RobertsSharon Byers
May 19, 2009·American Journal of Medical Genetics. Part a·Carmela Di DomenicoPaola Di Natale
Jan 30, 2010·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Silvia Muro
Apr 14, 2016·Molecular Therapy. Methods & Clinical Development·Graça Almeida-PoradaChristopher D Porada
May 17, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Yong Hong ChenBeverly L Davidson
Sep 19, 2008·Journal of Neuropathology and Experimental Neurology·Raquel M WaltonJohn H Wolfe
Nov 16, 2014·Cognitive, Affective & Behavioral Neuroscience·Benny B BriesemeisterMario Braun
Dec 2, 2010·Biochemical Society Transactions·Ahad A RahimSimon N Waddington
Nov 18, 2018·Italian Journal of Pediatrics·Alessandro FraldiMaria Ester Bernardo
May 1, 2020·Current Stem Cell Reports·Martin RodriguezGraҫa Almeida-Porada

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