RAG1 gene therapy
Research type
Research Study
Full title
Phase I/II Clinical Trial of autologous hematopoietic stem cell gene therapy in RAG1-deficient severe combined immunodeficiency (SCID)
IRAS ID
1007123
Contact name
Claire Booth
Contact email
Sponsor organisation
Leiden University Medical Center
Eudract number
2019-002343-14
Clinicaltrials.gov Identifier
Research summary
RAG1-deficient severe combined immunodeficiency (RAG1-SCID) is a genetic disorder that affects both boys and
girls. It is caused by errors in a gene that affects part of the immune system. The basic defect lies in the development
and function of cells of the immune system known as lymphocytes. These are crucial for the protection against
infections. In their absence, children are highly likely to develop serious infections, which they cannot fight properly.
Although some protection can be provided by drugs such as antibiotics, this is not effective for the long-term.
Fortunately, RAG1-SCID can be treated by hematopoietic stem cell transplantation (HSCT). For transplantation, the
donor’s bone marrow is matched to your child’s bone marrow to lower the risk of complications such as rejection. The
chances of success are very good (up to 80%) when a fully matched donor is available. However, the chance of
success is significantly lower when stem cells from less matched donors are used. Moreover, use of less matched
donors is associated with an increased risk of serious complications including graft versus host disease (when cells
from the donor see organs of the patient (recipient) as being different and attack them, which can cause problems in
the skin, gut, liver, lungs and the immune system itself).
An alternative option to HSCT is gene therapy where the aim is to deliver a normal copy of the gene that has been
identified as mutated and therefore responsible for a patient's RAG-1-SCID.
In several other variants of SCID, gene therapy with these lentiviruses has been proven safe and effective. The
purpose of this study is to test whether transplantation of gene-corrected stem cells is as effective as transplantation
of donor stem cells in subjects with RAG1-SCID.REC name
London - West London & GTAC Research Ethics Committee
REC reference
23/LO/0570
Date of REC Opinion
7 Dec 2023
REC opinion
Further Information Favourable Opinion