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| Name | Class |
|---|---|
| Fondazione Telethon | OTHER |
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This study investigated the safety and efficacy of different gene therapy approaches for Severe Combined Immunodeficiency (SCID) caused by the deficiency of adenosine deaminase (ADA) enzyme. This is a severe condition that can be cured by HLA-matched sibling donor bone marrow transplantation. Patients were enrolled if no HLA-identical sibling donor was available and the patient showed evidence of failure of enzyme replacement therapy or this treatment was not a long-term available option. The aim of the study was to evaluate the safety and efficacy of the procedure and to identify the relative role of peripheral blood lymphocytes and hematopoietic stem cells and progenitor cells in the long-term reconstitution of immune functions after retroviral vector mediated ADA gene transfer.
This is mono-centric, non-randomized, non-controlled, open label, phase I-II trial that evaluated the safety and efficacy of ADA gene transfer into somatic cells for the treatment of ADA-SCID
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PBL/HSC | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| gene transduced PBL and/or gene transduced HSC | Genetic | infusions of autologous PBL and/or HSC transduced with retroviral vectors encoding ADA |
|
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of safety of the administration of the autologous PBL and/or autologous HSC transduced with the normal human ADA gene |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of extent, kinetic and duration of the engraftment of transduced cells and the potential selective advantage of ADA positive cells | ||
| Evaluation of efficacy of the administration of autologous PBL/HSC(Clinical, immunological, hematological, microbiological, ADA activity and purine metabolism) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bordignon Claudio, MD | IRCCS San Raffaele | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22184407 | Derived | Sauer AV, Brigida I, Carriglio N, Hernandez RJ, Scaramuzza S, Clavenna D, Sanvito F, Poliani PL, Gagliani N, Carlucci F, Tabucchi A, Roncarolo MG, Traggiai E, Villa A, Aiuti A. Alterations in the adenosine metabolism and CD39/CD73 adenosinergic machinery cause loss of Treg cell function and autoimmunity in ADA-deficient SCID. Blood. 2012 Feb 9;119(6):1428-39. doi: 10.1182/blood-2011-07-366781. Epub 2011 Dec 19. | |
| 19652199 |
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| ID | Term |
|---|---|
| D016511 | Severe Combined Immunodeficiency |
| ID | Term |
|---|---|
| D000081207 | Primary Immunodeficiency Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
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| ID | Term |
|---|---|
| D015316 | Genetic Therapy |
| ID | Term |
|---|---|
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D005818 | Genetic Engineering |
| D005821 | Genetic Techniques |
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| To identify the relative role of peripheral blood lymphocytes and hematopoietic stem cells and progenitor cells in the long-term reconstitution of immune functions after gene therapy |
| Derived |
| Cassani B, Montini E, Maruggi G, Ambrosi A, Mirolo M, Selleri S, Biral E, Frugnoli I, Hernandez-Trujillo V, Di Serio C, Roncarolo MG, Naldini L, Mavilio F, Aiuti A. Integration of retroviral vectors induces minor changes in the transcriptional activity of T cells from ADA-SCID patients treated with gene therapy. Blood. 2009 Oct 22;114(17):3546-56. doi: 10.1182/blood-2009-02-202085. Epub 2009 Aug 3. |
| 19633200 | Derived | Sauer AV, Mrak E, Hernandez RJ, Zacchi E, Cavani F, Casiraghi M, Grunebaum E, Roifman CM, Cervi MC, Ambrosi A, Carlucci F, Roncarolo MG, Villa A, Rubinacci A, Aiuti A. ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency. Blood. 2009 Oct 8;114(15):3216-26. doi: 10.1182/blood-2009-03-209221. Epub 2009 Jul 24. |
| 19179314 | Derived | Aiuti A, Cattaneo F, Galimberti S, Benninghoff U, Cassani B, Callegaro L, Scaramuzza S, Andolfi G, Mirolo M, Brigida I, Tabucchi A, Carlucci F, Eibl M, Aker M, Slavin S, Al-Mousa H, Al Ghonaium A, Ferster A, Duppenthaler A, Notarangelo L, Wintergerst U, Buckley RH, Bregni M, Marktel S, Valsecchi MG, Rossi P, Ciceri F, Miniero R, Bordignon C, Roncarolo MG. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med. 2009 Jan 29;360(5):447-58. doi: 10.1056/NEJMoa0805817. |
| 18218852 | Derived | Cassani B, Mirolo M, Cattaneo F, Benninghoff U, Hershfield M, Carlucci F, Tabucchi A, Bordignon C, Roncarolo MG, Aiuti A. Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patients. Blood. 2008 Apr 15;111(8):4209-19. doi: 10.1182/blood-2007-05-092429. Epub 2008 Jan 24. |
| D049914 | DNA Repair-Deficiency Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D008919 |
| Investigative Techniques |