Retroviral mediated transfer of the cDNA for human glucocerebrosidase into hematopoietic stem cells of patients with gaucher disease. A phase I study

Cynthia Dunbar, Donald Kohn, Stefan Karlsson, Norman Barton, Roscoe Brady, Michele Cottler-Fox, Gay Crooks, Robert Emmons, Joan Esplin, Susan Leitman, Carl Lenarsky, Jan Nolta, Robertson Parkman, Michael Pensiero, Raphael Schifmann, Paul Tolstoshev, Kenneth Weinberg

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Patients with Gaucher disease suffer from a lack of functional glucocerebrosidase enzyme (Gc). Disease symptoms are a result of macrophage engorgement secondary to this enzyme deficiency. This study is designed to determine if cDNA encoding normal Gc can be introduced into macrophage precursors using a retroviral vector. CD34 + cells obtained from G-CSF mobilized peripheral blood stem cells or from bone marrow will be transduced ex vivo using one of the following three methods of transduction: 1) GlGc retroviral supernatant in the presence of autologous stroma over a period of 72 hours, 2) GlGc retroviral supernatant in the presence of interleukin-3, interleukin-6, stem cell factor and autologous stroma over a 72 hour period, 3) GlGc retroviral supernatant in the presence of interleukin-3, interleukin-6, and stem cell factor over a 72 hour period. These transduced cells will be reinfused into the patient and the patient monitored for toxicities as well as evidence of successful gene transfer and expression. A total of twenty-four patients will be enrolled on the protocol. Patients will be assigned in equal numbers to each of six groups. The two sites participating are the National Institutes of Health and Childrens Hospital of Los Angeles.

Original languageEnglish (US)
Pages (from-to)231-253
Number of pages23
JournalHuman Gene Therapy
Volume7
Issue number2
StatePublished - Jan 20 1996
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Dunbar, C., Kohn, D., Karlsson, S., Barton, N., Brady, R., Cottler-Fox, M., Crooks, G., Emmons, R., Esplin, J., Leitman, S., Lenarsky, C., Nolta, J., Parkman, R., Pensiero, M., Schifmann, R., Tolstoshev, P., & Weinberg, K. (1996). Retroviral mediated transfer of the cDNA for human glucocerebrosidase into hematopoietic stem cells of patients with gaucher disease. A phase I study. Human Gene Therapy, 7(2), 231-253.