NEW YORK (Reuters Health) - Gene therapy to correct the abnormal common cytokine-receptor gamma chain (gamma-c) that causes X-linked severe combine immunodeficiency (SCID-X1) restores functional cellular and humoral immunity, according to a paper in the December 18/25 issue of The Lancet.
In fact, prophylactic medication could be discontinued for two of the four patients included in this phase I/II trial, Dr. Adrian J. Thrasher, at University College London, and his multinational research team report.
Autologous CD34-positive hematopoietic bone-marrow stem cells were transduced with human gamma-c cloned into a gibbon-ape-leukemia virus pseudotyped gamma-retroviral vector and then administered back to the patients, who ranged in age from 4 to 33 months.
Natural killer cells appeared within 4 weeks of treatment, and “have persisted at the lower end of the normal ranges for age-matched controls.” Viral or opportunistic infections have been cleared, and growth and development has been normal.
In the two patients no longer requiring chemical prophylaxis, normal numbers of cells expressing CD3, CD4 and CD8 have also been achieved.
At last follow-up, between 12 and 29 months, “all patients were at home in normal family and social environments, without restriction on activities or exposure,” reports Dr. Thrasher’s team.
“With improved protocols and more sophisticated vector configurations, there is potential to establish gene therapy as a standard therapeutic procedure for this type of disease,” they conclude.
In a related commentary, Drs. Marina Cavazzana-Calvo and Alain Fischer, from Hopital Necker-Enfants Malades in Paris, note that altogether, there have now been 18 cases of SCID that have been treated with a retroviral-mediated gene-transfer protocol, 17 of whom derived “clear and sustained clinical benefits.”
They suggest that the higher transduced rate achieved in B and myeloid cells in the current report result from the avoidance of fetal calf serum in the culture medium and use of the gibbon-leukemia-virus envelope.
“Overall, the available reports of gene therapy’s efficacy in SCID-X1 and ADA deficiency should encourage researchers to extend the treatment to target other life-threatening immunodeficiencies and, possibly, other genetic diseases of the hematopoietic system,” the editorialists conclude.
Source: Lancet 2004;364:2155-2156,2181-2187. [ Google search on this article ]
MeSH Headings:Biological Factors: Biological Therapy: Bone Marrow Cells: Chemotactic Factors: Genetic Engineering: Genetic Techniques: Hematopoietic Stem Cells: Immunity, Cellular: Immunologic and Biological Factors: Immunologic Factors: Membrane Proteins: Investigative Techniques: Receptors, Cell Surface: Receptors, Immunologic: Therapeutics: Gene Therapy: Receptors, Cytokine: Chemokines: Chemokines, C: Chemical Actions and Uses: Chemical Actions: Analytical, Diagnostic and Therapeutic Techniques and Equipment: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
