Linked Life Data

9853529

Source:http://linkedlifedata.com/resource/pubmed/id/9853529

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
1999-2-26
pubmed:abstractText
Retroviral gene transfer of the glucocerebrosidase gene to hematopoietic progenitor and stem cells has shown promising results in animal models and corrected the enzyme deficiency in cells from Gaucher patients in vitro. Therefore, a clinical protocol was initiated to explore the safety and feasibility of retroviral transduction of peripheral blood (PB) or bone marrow (BM) CD34+ cells with the G1Gc vector. This vector uses the viral LTR promoter to express the human glucocerebrosidase cDNA. Three adult patients have been entered with follow-up of 6-15 months. Target cells were G-CSF-mobilized and CD34-enriched PB cells or CD34-enriched steady state BM cells, and were transduced ex vivo for 72 hr. Patient 1 had PB cells transduced in the presence of autologous stromal marrow cells. Patient 2 had PB cells transduced in the presence of autologous stroma, IL-3, IL-6, and SCF. Patient 3 had BM cells transduced in the presence of autologous stroma, IL-3, IL-6, and SCF. At the end of transduction, the cells were collected and infused immediately without any preparative treatment of the patients. The transduction efficiency of the CD34+ cells at the end of transduction was approximately 1, 10, and 1 for patients 1, 2, and 3, respectively, as estimated by semiquantitative PCR on bulk samples and PCR analysis of individual hematopoietic colonies. Gene marking in vivo was demonstrated in patients 2 and 3. Patient 2 had vector-positive PB granulocytes and mononuclear bone marrow cells at 1 month postinfusion and positive PB mononuclear cells at 2 and 3 months postinfusion. Patient 3 had a positive BM sample at 1 month postinfusion but was negative thereafter. These results indicate that gene-marked cells can engraft and persist for at least 3 months postinfusion, even without myeloablation. However, the level of corrected cells (<0.02%) is too low to result in any clinical benefit, and glucocerebrosidase enzyme activity did not increase in any patient following infusion of transduced cells. Modifications of vector systems and transduction conditions, along with partial myeloablation to allow higher levels of engraftment, may be necessary to achieve beneficial levels of correction in patients with Gaucher disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2629-40
pubmed:dateRevised
2010-12-28
pubmed:meshHeading
pubmed-meshheading:9853529-Adult, pubmed-meshheading:9853529-Antigens, CD34, pubmed-meshheading:9853529-Base Sequence, pubmed-meshheading:9853529-Bone Marrow Cells, pubmed-meshheading:9853529-DNA Primers, pubmed-meshheading:9853529-Female, pubmed-meshheading:9853529-Gaucher Disease, pubmed-meshheading:9853529-Gene Therapy, pubmed-meshheading:9853529-Gene Transfer Techniques, pubmed-meshheading:9853529-Genetic Vectors, pubmed-meshheading:9853529-Glucosylceramidase, pubmed-meshheading:9853529-Granulocyte Colony-Stimulating Factor, pubmed-meshheading:9853529-Hematopoietic Stem Cell Mobilization, pubmed-meshheading:9853529-Humans, pubmed-meshheading:9853529-Male, pubmed-meshheading:9853529-Retroviridae, pubmed-meshheading:9853529-Stromal Cells, pubmed-meshheading:9853529-Transduction, Genetic
pubmed:year
1998
pubmed:articleTitle
Retroviral transfer of the glucocerebrosidase gene into CD34+ cells from patients with Gaucher disease: in vivo detection of transduced cells without myeloablation.
pubmed:affiliation
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't