Rare Disease Report

ADA-SCID (aka Bubble Baby Disease) Cured by Gene Therapy

APRIL 05, 2017
James Radke
A study published in in the Journal of Clinical Investigation revealed that gene therapy cured 9 of 10 children with adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID, aka Bubble Babyy Disease). Children in the ground-breaking Phase 2 study were treated at Mattel Children’s Hospital in Los Angeles, CA (n=7) or NIH’s National Human Genome Research Institute in Bethesda, MD (n=3). The clinical trial ran from 2009 to 2012.
 
ADA-SCID or bubble baby disease, is caused by a genetic mutation that results in the lack of the adenosine deaminase. Without the enzyme, immune cells are not able to properly fight infections and children must remain isolated in clean and germ-free environments.
 
The preferred treatment option for ADA-SCID patients is allogeneic hematopoietic stem cell transplantation (HSCT) with a matched family donor. Enzyme replacement therapy (ERT; Andagen) with polyethylene-conjugated ADA is also used but its efficacy is variability and it can be very costly.

Methods

The gene therapy involved blood stem cells being removed from each child’s bone marrow to which a functional gene for synthesizing adenosine deaminase enzyme was inserted. Each child then received a transplant of their own corrected blood stem cells.
 
 
 
Subject Months on ERT Age at Transplant
(months)
Follow--up time
(months)
401
402
403
404
405
406
407
408
409
410
173
3
90
3
8
17
14
3
5
2
184
4
97
3
8
17
14
3
20
3
84
80
72
60
60
54
54
54
42
42

 

Results

Of the 10 patients, 9 showed sustained benefits from the gene therapy and had sufficient immune reconstitution to remain in good health, free of infections, with normal growth and development, and without need to resume ERT (twice weekly) or have a bone marrow transplant.
 
The one patient who did not respond to gene therapy was also the oldest patient in the study. The patient was 15 years old at the time of treatment and they had to resume ERT by 6 months after the procedure due to absence of evidence of immune recovery after gene therapy.

Immunological Outcomes
 Subject ERT Prophylactic
antibiotics
i.v. lg RT
401
402
403
404
405
406
407
408
409
410
yes
no
no
no
no
no
no
no
no
no
yes
no
yes
no
no
yes
yes
no
yes
no
yes
yes
yes
no
yes
yes
yes
no
yes
no

Reference

Shaw KL, Garabedian E, Mishra S, et al. Clinical efficacy of gene-modified stem cells in adenosine deaminase–deficient immunodeficiency. J Clin Invest. 2017. doi:10.1172/JCI90367


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