Gene therapy is an experimental treatment currently available for children with ADA-SCID, X-linked SCID, and Artemis SCID. Families of children who choose this therapy must enroll in a clinical trial.
There are several clinical trials now taking place at children’s hospitals throughout the United States and at the National Institute of Health. Research clinical trials that are available at https://clinicaltrials.gov/.
In all cases of SCID, there is a severe reduction in the number of T cells. With gene therapy, doctors fix the child's abnormal hematopoietic stem cells, so that they make normal numbers of T cells. After doctors fix the hematopoietic stem cells, they infuse the hematopoietic stem cells back into the child to create a functional immune system. These are the steps in gene therapy treatment process.
- The abnormal hematopoietic stem cells (containing the mutated gene) are extracted from the blood or bone marrow of the of the child and sent to the laboratory where the they will be fixed.
- In the lab, doctors make copies of the gene that caused the SCID. These copies are normal genes and do not contain the mutation. The normal gene is then put into a virus, which has been deactivated and can no longer spread infection, but is very efficient in penetrating hematopoetic stem cells.
- In the lab, doctors mix the virus, containing the normal gene, with the patient’s hematopoietic stem cells. The virus penetrates into the hematopoietic stem cells and the normal gene becomes a permanent part of the hematopoietic stem cell and is copied into other cells when the cell divides. The "corrected" hematopoietic stem cells are now able to make normal T cells. These corrected hematopoietic stem cells are then placed into frozen storage.
- Before the corrected hematopoietic stem cells are infused into the child, the child may or may not receive conditioning, such as chemotherapy or other immuno-suppressant drugs. This is sometimes needed to make sure the corrected hematopoietic stem cells have sufficient space in the bone marrow to grow and divide normally.
- The corrected hematopoietic stem cells are taken out of storage, and are given back to the child in a simple IV infusion. In two to three months, the corrected hematopoietic stem cells spread throughout the child’s body, which results in a new, healthy immune system with normal T cells.
One past concern with gene therapy is that it could cause leukemia, which is a cancer of the blood, or bone marrow. The reason for this concern is because in gene therapy trials for X-linked SCID conducted in Europe between 1999 and 2006, the virus, or vector, that carried the corrected gene caused leukemia in five of the 20 boys enrolled in the trial. Doctors treated the five patients and one died. In 2016, one additional patient on this trial developed lymphoma caused by the gene therapy.
Since those trials, to address the safety concerns, scientists have changed the type of virus, or vector, used to deliver the corrected gene. In trials of X-linked SCID using new modified viruses, or vectors, leukemia and lymphoma have not been seen. Patients with ADA-SCID who have undergone gene therapy have never been reported to have leukemia.
Scientists think that the chance of developing leukemia from gene therapy using the newer vectors is extremely low, but many more years of follow-up are needed to be sure.
Another risk is that there is a possibility that the gene therapy does not result in a good immune system for the child. Successful patient outcomes have resulted from gene therapy; however, as with any experimental treatment, this cannot be guaranteed for all participants.