Gene Therapy for ADA-SCID

Conditions

Severe Combined Immunodeficiency Syndrome

Keywords

adenosine deaminase, SCID, gene therapy, retroviral vector

Brief summary

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.

Detailed description

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

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.

2009-08-0351 citations

10.1182/blood-2009-02-202085

Gene therapy for immunodeficiency due to adenosine deaminase deficiency.

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.

2009-01-01671 citations

10.1056/nejmoa0805817

Interventions

GENETICgene transduced PBL and/or gene transduced HSC

infusions of autologous PBL and/or HSC transduced with retroviral vectors encoding ADA

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Healthy volunteers

No

Inclusion criteria

* Lack of HLA-identical sibling donor and * Evidence of failure of the enzyme replacement treatment after \>6 months or * PEG-ADA is not available as a life long option

Exclusion criteria

* HLA identical bone marrow sibling donor * HIV infection * Malignancy

Design outcomes

Primary

Measure	Time frame
Evaluation of safety of the administration of the autologous PBL and/or autologous HSC transduced with the normal human ADA gene	—

Secondary

Measure	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)	—
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	—

Outcome results

None listed