Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiency

@article{Ferrua2010UpdateOG,
  title={Update on gene therapy for adenosine deaminase-deficient severe combined immunodeficiency},
  author={Francesca Ferrua and Immacolata Brigida and Alessandro Aiuti},
  journal={Current Opinion in Allergy and Clinical Immunology},
  year={2010},
  volume={10},
  pages={551–556}
}
Purpose of reviewThe present review describes the recent progress in the treatment of adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) using autologous gene-modified hematopoietic stem cells, comparing immune reconstitution with respect to allogeneic transplant and discussing differences with gene therapy for SCID-X1. Recent findingsSince 2000, more than 30 ADA-SCID patients have been treated with gene therapy worldwide, with successful outcome in most cases, consisting… 

Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency.

Treatment of ADA-SCID with ex vivo lentiviral HSPC gene therapy resulted in high overall and event-free survival with sustained ADA expression, metabolic correction, and functional immune reconstitution.

Gene therapy for primary adaptive immune deficiencies.

Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy.

After HSC-GT, ADA-SCID patients displayed quasi-normal early B cell tolerance checkpoints, as evidenced by restored removal of developing autoreactive and ANA-expressing B cells, suggesting ADA plays an essential role in controlling autore active B cell counterselection by regulating BCR and TLR functions.

Autoimmune Dysregulation and Purine Metabolism in Adenosine Deaminase Deficiency

The value of the ADA-deficient mouse model as a useful tool to study both immune and metabolic disease mechanisms and the lymphocyte subpopulations particularly prone to contribute to the loss of self-tolerance and onset of autoimmunity in ADA deficiency are assessed.

Adenosine Deaminase Deficiency – More Than Just an Immunodeficiency

This review will outline the impact of ADA deficiency on various organ systems, starting with the well-understood immunological abnormalities and suggest that it should be recognized as a systemic metabolic disorder that affects multiple organ systems.

Hematopoietic stem cell expansion and gene therapy.

Some of the current limitations of HSC gene therapy could be overcome by combining novel HSC expansion strategies with gene therapy, as well as the opportunities presented by implementing ex vivo expansion of gene-modified HSC.
...

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