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: Takayuki Yokoi, Kentarou Yokoi, Kazumasa Akiyama, Takashi Higuchi, Yohta Shimada, Hiroshi Kobayashi, Taku Sato, Toshiaki Ohteki, Makoto Otsu, Hiromitsu Nakauchi, Hiroyuki Ida, Toya Ohashi
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 119 Issue 3 Pg. 232-238 (11 2016) ISSN: 1096-7206 [Electronic] United States
• PMID: 27590924 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016. Published by Elsevier Inc.

Chemical References

• Antibodies, Anti-Idiotypic
• Glycoproteins
• IDS protein, human
• Dermatan Sulfate
• Heparitin Sulfate
• Proto-Oncogene Proteins c-kit

Topics

• Animals
• Antibodies, Anti-Idiotypic (administration & dosage)
• Bone Marrow Transplantation
• Dermatan Sulfate (metabolism)
• Disease Models, Animal
• Glycoproteins (genetics)
• Heparitin Sulfate (metabolism)
• Humans
• Lysosomes (enzymology, pathology)
• Mice
• Mice, Knockout
• Mucopolysaccharidosis II (immunology, metabolism, pathology, therapy)
• Proto-Oncogene Proteins c-kit (antagonists & inhibitors, immunology)