Faculty Collaboration Database

Autologous transplantation of lentivector/acid ceramidase-transduced hematopoietic cells in nonhuman primates. Hum Gene Ther 2011 Jun;22(6):679-87

Date

02/02/2011

Pubmed ID

21280983

Pubmed Central ID

PMC3155125

DOI

10.1089/hum.2010.195

Scopus ID

2-s2.0-79958209082 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

Farber disease is a rare lysosomal storage disorder (LSD) that manifests due to acid ceramidase (AC) deficiencies and ceramide accumulation. We present a preclinical gene therapy study for Farber disease employing a lentiviral vector (LV-huAC/huCD25) in three enzymatically normal nonhuman primates. Autologous, mobilized peripheral blood (PB) cells were transduced and infused into fully myelo-ablated recipients with tracking for at least 1 year. Outcomes were assessed by measuring the AC specific activity, ceramide levels, vector persistence/integration, and safety parameters. We observed no hematological, biochemical, radiological, or pathological abnormalities. Hematological recovery occurred by approximately 3 weeks. Vector persistence was observed in PB and bone marrow (BM) cells by qualitative and quantitative PCR. We did not observe any clonal proliferation of PB and BM cells. Importantly, AC-specific activity was detected above normal levels in PB and BM cells analyzed post-transplantation and in spleens and livers at the endpoint of the study. Decreases of ceramide in PB cells as well as in spleen and liver tissues were seen. We expect that this study will provide a roadmap for implementation of clinical gene therapy protocols targeting hematopoietic cells for Farber disease and other LSDs.

Author List

Walia JS, Neschadim A, Lopez-Perez O, Alayoubi A, Fan X, Carpentier S, Madden M, Lee CJ, Cheung F, Jaffray DA, Levade T, McCart JA, Medin JA

Author

Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acid Ceramidase
Animals
Farber Lipogranulomatosis
Genetic Therapy
Genetic Vectors
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Lentivirus
Macaca mulatta
Male
Transduction, Genetic
Transplantation, Autologous