Bone Marrow Transplantation for Feline Mucopolysaccharidosis I

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dc.contributor.authorAguirre, Gustavo D
dc.contributor.authorEllinwood, Norman Matthew
dc.contributor.authorVite, Charles H
dc.contributor.authorColle, Marie-Anne
dc.contributor.authorWeil, Margaret A
dc.contributor.authorCasal, Margret L
dc.contributor.authorVite, Charles H
dc.contributor.authorWiemelt, Staci
dc.contributor.authorHasson, Christopher W
dc.contributor.authorO'Malley, Thomas M
dc.contributor.authorHe, Xingxuan
dc.contributor.authorProciuk, Ulana
dc.contributor.authorEvans, Sydney M
dc.contributor.authorMelniczek, John R
dc.contributor.authorLannon, Anne
dc.contributor.authorKnox, Van W
dc.contributor.authorHaskins, Mark E
dc.contributor.authorVanier, Marie T
dc.contributor.authorSchuchman, Edward H
dc.contributor.authorWalkley, Steven U
dc.contributor.authorHaskins, Mark E
dc.date2023-05-17T11:20:00.000
dc.date.accessioned2023-05-23T04:44:16Z
dc.date.available2023-05-23T04:44:16Z
dc.date.issued2007-07-01
dc.date.submitted2015-04-08T14:00:04-07:00
dc.description.abstractSevere mucopolysaccharidosis type I (MPS I) is a fatal neuropathic lysosomal storage disorder with significant skeletal involvement. Treatment involves bone marrow transplantation (BMT), and although effective, is suboptimal, due to treatment sequelae and residual disease. Improved approaches will need to be tested in animal models and compared to BMT. Herein we report on bone marrow transplantation to treat feline mucopolysaccharidosis I (MPS I). Five MPS I stably engrafted kittens, transplanted with unfractionated bone marrow (6.3 × 107–1.1 × 109 nucleated bone marrow cells per kilogram) were monitored for 13–37 months post-engraftment. The tissue total glycosaminoglycan (GAG) content was reduced to normal levels in liver, spleen, kidney, heart muscle, lung, and thyroid. Aorta GAG content was between normal and affected levels. Treated cats had a significant decrease in the brain GAG levels relative to untreated MPS I cats and a paradoxical decrease relative to normal cats. The α-l-iduronidase (IDUA) activity in the livers and spleens of transplanted MPS I cats approached heterozygote levels. In kidney cortex, aorta, heart muscle, and cerebrum, there were decreases in GAG without significant increases in detectable IDUA activity. Treated animals had improved mobility and decreased radiographic signs of disease. However, significant pathology remained, especially in the cervical spine. Corneal clouding appeared improved in some animals. Immunohistochemical and biochemical analysis documented decreased central nervous system ganglioside storage. This large animal MPS I study will serve as a benchmark of future therapies designed to improve on BMT.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/48858
dc.legacy.articleid1110
dc.legacy.fields10.1016/j.ymgme.2007.03.001
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1110&context=vet_papers&unstamped=1
dc.rights<p>NOTICE: This is the author’s version of a work that was accepted for publication in Molecular Genetics and Metabolism. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Molecular Genetics and Metabolism, 91, 3, <a href="http://dx.doi.org/10.1016/j.ymgme.2007.03.001" id="x-x-ddDoi">10.1016/j.ymgme.2007.03.001</a>.</p>
dc.source.beginpage239
dc.source.endpage250
dc.source.issue100
dc.source.issue3
dc.source.journalDepartmental Papers (Vet)
dc.source.journaltitleMolecular Genetics and Metabolism
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume91
dc.subject.otherbone marrow transplantation
dc.subject.otherdisease models
dc.subject.otheranimal
dc.subject.otherlysosomal storage diseases
dc.subject.otheriduronidase
dc.subject.otherglycosaminoglycans
dc.subject.othermucopolysaccharidosis I
dc.subject.otherDisease Modeling
dc.subject.otherOsteopathic Medicine and Osteopathy
dc.subject.otherVeterinary Medicine
dc.titleBone Marrow Transplantation for Feline Mucopolysaccharidosis I
dc.typeArticle
digcom.contributor.authorEllinwood, Norman Matthew
digcom.contributor.authorColle, Marie-Anne
digcom.contributor.authorWeil, Margaret A
digcom.contributor.authorCasal, Margret L
digcom.contributor.authorisAuthorOfPublication|email:vite@vet.upenn.edu|institution:University of Pennsylvania|Vite, Charles H
digcom.contributor.authorWiemelt, Staci
digcom.contributor.authorHasson, Christopher W
digcom.contributor.authorO'Malley, Thomas M
digcom.contributor.authorHe, Xingxuan
digcom.contributor.authorProciuk, Ulana
digcom.contributor.authorVerot, Lucie
digcom.contributor.authorMelniczek, John R
digcom.contributor.authorLannon, Anne
digcom.contributor.authorisAuthorOfPublication|email:gda@vet.upenn.edu|institution:University of Pennsylvania|Aguirre, Gustavo D
digcom.contributor.authorKnox, Van W
digcom.contributor.authorisAuthorOfPublication|email:sydevans@mail.med.upenn.edu|institution:University of Pennsylvania|Evans, Sydney M
digcom.contributor.authorVanier, Marie T
digcom.contributor.authorSchuchman, Edward H
digcom.contributor.authorWalkley, Steven U
digcom.contributor.authorisAuthorOfPublication|email:mhaskins@vet.upenn.edu|institution:University of Pennsylvania|Haskins, Mark E
digcom.identifiervet_papers/100
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upenn.schoolDepartmentCenterDepartmental Papers (Vet)
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