title: Non-myeloablative preconditioning with ACK2 (anti-c-kit antibody) is efficient in bone marrow transplantation for murine models of mucopolysaccharidosis type II.
abstract: Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disease caused by the deficient activity of iduronate 2-sulfatase (IDS), which is involved in the lysosomal catabolism of the glycosaminoglycans (GAGs) dermatan and heparan sulfate. Such a deficiency leads to the accumulation of undegraded GAGs in some organs. Although enzyme replacement therapy is available as a treatment of MPS II, there are some limitations, such as the requirement of weekly administration for whole life. To avoid such limitations, hematopoietic cell transplantation (HSCT) is a possible alternative. In fact, some report suggested positive effects of HSCT for MPS II. However, HSCT has also some limitations. Strong conditioning regimens can cause severe side effects. For overcome this obstacle, we studied the efficacy of ACK2, an antibody that blocks KIT, followed by low-dose irradiation as a preconditioning regimen for HSCT using a murine model of MPS II. This protocol achieves 58.7±4.92% donor chimerism at 16weeks after transplantation in the peripheral blood of recipient mice. GAG levels were significantly reduced in liver, spleen, heart and intestine. These results indicated that ACK2-based preconditioning might be one of the choices for MPS II patients who receive HSCT.
authors: Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: tyokoi@kcmc.jp.
authors: Takayuki
authors: T
authors: Yokoi
authors: Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
authors: Kentarou
authors: K
authors: Yokoi
authors: Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Department of Pediatrics, The Kitasato University School of Medicine, Kanagawa, Japan.
authors: Kazumasa
authors: K
authors: Akiyama
authors: Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
authors: Takashi
authors: T
authors: Higuchi
authors: Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
authors: Yohta
authors: Y
authors: Shimada
authors: Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Kobayashi
authors: Department of Biodefense Research Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Taku
authors: T
authors: Sato
authors: Department of Biodefense Research Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Toshiaki
authors: T
authors: Ohteki
authors: Division of Stem Cell Therapy, Center for Stem Cell and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors: Makoto
authors: M
authors: Otsu
authors: Division of Stem Cell Therapy, Center for Stem Cell and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Hiromitsu
authors: H
authors: Nakauchi
authors: Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Ida
authors: Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan; Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
authors: Toya
authors: T
authors: Ohashi
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation; D003871:Dermatan Sulfate / Q000378:metabolism; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000235:genetics; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000201:enzymology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016532:Mucopolysaccharidosis II / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D003871:Dermatan Sulfate; D006023:Glycoproteins; D006497:Heparan Sulfate; D019009:Proto-Oncogene Proteins c-kit; C018322:IDS protein, human
keywords: ACK2; Hematopoietic cell transplantation; Mucopolysaccharidosis type II; Non-myeloablative preconditioning