Correction of ADA-SCID by Stem Cell Gene Therapy Combined with Nonmyeloablative Conditioning

@article{Aiuti2002CorrectionOA,
  title={Correction of ADA-SCID by Stem Cell Gene Therapy Combined with Nonmyeloablative Conditioning},
  author={Alessandro Aiuti and Shimon Slavin and Memet Aker and Francesca Ficara and Sara Deola and Alessandra Mortellaro and Shoshana Morecki and Grazia Andolfi and Antonella Tabucchi and Filippo Carlucci and Enrico Marinello and Federica Cattaneo and Sergio Vai and Paolo Servida and Roberto Miniero and Maria Grazia Roncarolo and Claudio Bordignon},
  journal={Science},
  year={2002},
  volume={296},
  pages={2410 - 2413}
}
Hematopoietic stem cell (HSC) gene therapy for adenosine deaminase (ADA)–deficient severe combined immunodeficiency (SCID) has shown limited clinical efficacy because of the small proportion of engrafted genetically corrected HSCs. We describe an improved protocol for gene transfer into HSCs associated with nonmyeloablative conditioning. This protocol was used in two patients for whom enzyme replacement therapy was not available, which allowed the effect of gene therapy alone to be evaluated… Expand
Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning.
TLDR
It is document successful reconstitution of immune function in a child with the adenosine deaminase (ADA)-deficient form of severe combined immunodeficiency (SCID) following hematopoietic stem cell (HSC) gene therapy. Expand
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TLDR
Stem cell gene therapy combined with appropriate conditioning regimens might be extended to other genetic disorders of the hematopoietic system. Expand
A Tale of Two SCIDs
TLDR
Two new reports in this issue of Science Translational Medicine add to the accumulating findings from gene therapy trials in Italy, France, and the United States that show clinical benefits of this alternative treatment. Expand
Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiency
TLDR
In comparison with SCID-X1, ADA-SCID gene therapy presents a better safety profile and engraftment of multilineage transduced stem/progenitor cells, thanks to the use of nonmyeloablative preconditioning. Expand
Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency
TLDR
The developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells are discussed. Expand
Treating Immunodeficiency through HSC Gene Therapy.
TLDR
Targeted gene editing allowing precise DNA correction via platforms such as ZFNs, TALENs and CRISPR/Cas9 may now offer promising strategies to improve the safety and efficacy of gene therapy in the future. Expand
Immunoresponse to Gene-Modified Hematopoietic Stem Cells
TLDR
Preclinical and clinical data indicate that myeloablative total body irradiation (TBI) allows for efficient engraftment and tolerance to gene-modified HSCs, and new gene editing and in vivo gene therapy techniques could pose additional immune concerns compared to ex vivo gene Therapy methods. Expand
Gene Therapy for Primary Immunodeficiencies
TLDR
Clinical trials for SCID-X1, Wiskott-Aldrich syndrome, and recently ADA-SCID showed sustained engraftment of gene-corrected cells, restored immune function, and general improvement of clinical condition, with a positive safety profile, so continuous monitoring will be important to confirm long-term safety and efficacy. Expand
Clinical efficacy of gene-modified stem cells in adenosine deaminase–deficient immunodeficiency
TLDR
Clinical therapeutic efficacy from gene therapy for ADA-deficient SCID is demonstrated with an excellent clinical safety profile, and no patient has developed a leukoproliferative disorder or other vector-related clinical complication since transplant. Expand
Ten years of gene therapy for primary immune deficiencies.
  • A. Aiuti, M. Roncarolo
  • Biology, Medicine
  • Hematology. American Society of Hematology. Education Program
  • 2009
TLDR
Following recent advances in preclinical studies, lentiviral vectors are now being translated into new clinical approaches, such as Wiskott-Aldrich Syndrome, and will provide significant advantages in terms of natural gene regulation and reduction in the potential for adverse mutagenic events. Expand
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