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Successful Low-Risk Hematopoietic Cell Therapy in a Mouse Model of Type 1 Gaucher Disease

In English

Författare

Summary, in English

Hematopoietic stem cell-based gene therapy offers the possibility of permanent correction for genetic disorders of the hematopoietic system. However, optimization of present protocols is required before gene therapy can be safely applied as general treatment of genetic diseases. In this study we have used a mouse model of type 1 Gaucher disease (GD) to demonstrate the feasibility of a low-risk conditioning regimen instead of standard radiation, which is associated with severe adverse effects. We first wanted to establish what level of engraftment and glucosylceramidase (GCase) activity is required to correct the pathology of the type 1 GD mouse. Our results demonstrate that a median wild-type (WT) cell engraftment of 7%, corresponding to GCase activity levels above 10 nmoles/hour and mg protein, was sufficient to reverse pathology in bone marrow and spleen in the GD mouse. Moreover, we applied nonmyeloablative doses of busulfan as a pretransplant conditioning regimen and show that even WT cell engraftment in the range of 1%-10% can confer a beneficial therapeutical outcome in this disease model. Taken together, our data provide encouraging evidence for the possibility of developing safe and efficient conditioning protocols for diseases that require only a low level of normal or gene-corrected cells for a permanent and beneficial therapeutic outcome. STEM CELLS 2009; 27: 744-752

Publiceringsår

2009

Språk

Engelska

Sidor

744-752

Publikation/Tidskrift/Serie

Stem Cells

Volym

27

Issue

3

Dokumenttyp

Artikel i tidskrift

Förlag

AlphaMed Press

Ämne

  • Cell and Molecular Biology

Nyckelord

  • Hematopoietic stem cell
  • Gaucher disease
  • Disease model
  • transplantation
  • Busulfan

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1549-4918