Why was gene therapy developed for X-SCID?
is fatal unless treated. The conventional treatment is bone marrow
transplantation, which has excellent results with a full matched donor,
but less satisfactory results with a poorer match. Only one third of
X-SCID patients will have a fully matched donor. Bone marrow
transplantation involves powerful chemotherapy and regrettably, up to 20
per cent of children transplanted with a less than full match die. Gene
therapy has therefore been a highly valuable treatment option for this
group of children.
In gene therapy, a working copy of the
defective gene is placed in the child’s own bone marrow cells and these
are then returned to the child. The gene is placed in the cells using a
vector, a modified virus. Modified cells grow rapidly and ensure that
the child’s immune function returns, sometimes completely.
X-SCID gene therapy and leukaemia
similar X-SCID trial in Paris led to a number of children developing
leukaemia (four cases from 11 treated). Three were treated and
recovered, one, unfortunately, died. There is no doubt in the Paris
cases that the leukaemia was caused by the gene therapy, where the
introduced gene was implanted next to, and switched on, an oncogene (a
cancer causing gene).
The three other children are in remission
from leukaemia, their immune systems are now working again, and they are
doing very well.
We have now conducted a number of molecular
tests and can demonstrate that our case of leukaemia was also caused by
the gene therapy. The actual mechanism is similar to the cases in Paris
and further work is ongoing.
Families are carefully counselled
about the possible risks, and since the first Paris case, this has
included discussion of the possibility of leukaemia. We are extremely
thorough in seeking fully informed consent and all have been aware of
this risk before entering the study. In every case, we have required the
approval of the GTAC regulator before treating a patient and a number
of children including the present case received independent counselling
from a specialist outside of GOSH before treatment.
Prospects for the children who get leukaemia
is a very serious illness but can be treated and success rates now
exceed 80 per cent. Taking our results and Paris’ together, present
indications are that gene therapy is still safer and less intrusive than
the conventional treatment, for those children without a good bone
marrow donor match. Obviously as trials continue we will see how we can
minimise risks to patients through protocols and vector design.
current gene therapy treatment for X-SCID is being replaced by a new
vector which has been designed to reduce the risk. There are no plans to
use our old vector to treat future children.
No problems have been seen so far on the ada-SCID trial and patients are monitored closely.
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