An experimental form of gene therapy developed by a team of researchers from UCLA and Great
Ormond Street Hospital in London has successfully treated 48 of 50 children born with a rare
and deadly inherited disorder that leaves them without an immune system.
Severe combined immunodeficiency due to adenosine deaminase deficiency, or ADA-SCID, is caused
by mutations in the ADA gene that creates the enzyme adenosine deaminase, which is essential
to a functioning immune system.
For children with the condition, even day-to-day activities like going to school or playing
with friends can lead to dangerous, life-threatening infections.
If untreated, ADA-SCID can be fatal within the first two years of life.
The investigational gene therapy method involves first collecting some of the child’s blood-forming
stem cells, which have the potential to create all types of blood and immune cells.
Next, using an approach developed by the research team, a new copy of the ADA gene is delivered
into the stem cells by a modified lentivirus, or “viral vector.”
The corrected cells are then returned to the child’s body, where they are intended to
produce a continual supply of healthy immune cells capable of fighting infection.
In a study published in the journal New England Journal of Medicine, the researchers report
two- and three-year outcomes for children treated with the investigational lentiviral
gene therapy in clinical trials at GOSH, UCLA Mattel Children’s Hospital and the National
Institutes of Health between 2012 and 2017.
The researcher says that between all three clinical trials, 50 patients were treated,
and the overall results were very encouraging.
All the patients are alive and well, and in more than 95% of them, the therapy appears
to have corrected their underlying immune system problems.
No complications or treatment-limiting events were reported among the patients.
Most adverse events were mild or moderate, and were considered to be related to routine
procedures performed in preparation for the experimental gene therapy treatment or effects
of the immune system rebuilding.
Treatment was successful in all but two of the 50 cases, and both of those children were
able to return to current standard-of care-therapies and treatments, with one eventually receiving
a bone marrow transplant.
The investigational gene therapy — a one-time procedure that the researchers say may provide
lifelong results — is a welcome potential new treatment option for children with ADA-SCID,
who otherwise must undergo once- or twice-weekly injections of the ADA enzyme until a matched
bone marrow donor, usually a close family member, can be found.
If a donor is not available, patients require lifelong injections, along with antibiotics,
antifungal medications and monthly infusions of immunoglobulin, which contains infection-fighting
antibodies.
These treatments are expensive and therefore out of reach for patients in many countries.
If approved in the future, this treatment could be standard for ADA-SCID, and potentially
many other genetic conditions, removing the need to find a matched donor for a bone marrow
transplant and the toxic side effects often associated with that treatment.
Ten of the children in the UCLA study were treated using a frozen preparation of corrected
stem cells.
These children experienced similar outcomes to the children treated with cells that were
not frozen.
The freezing approach may allow children with ADA-SCID to have their stem cells collected
locally, then have them transported and processed at a manufacturing facility elsewhere and
shipped back to a specialized hospital near them, removing the need for patients and their
families to travel long distances to specialist centers.