Scientists from the National Institute of Allergy and Infectious Diseases (NIAID) have found that gene therapy can safely rebuild the immune systems of older children, adolescents, and young adults with a rare immunodeficiency disorder.

The disorder, called X-linked severe combined immunodeficiency (SCID-X1), is caused by mutations in the IL2RG gene and primarily affects males. It prevents infection-fighting immune cells from developing correctly; this means patients are highly susceptible to life-threatening infections. The research is set to be presented by Dr. Suk See De Ravin of the NIAID at The American Society of Hematology 57th Annual Meeting in Orlando, Fla.

Currently, stem cell transplants (ideally from a genetically-matched sibling donor) are the only lifesaving treatment for infants with SCID-X1. If a sibling match is unavailable, the baby can receive stem cells from a parent, but it will only partially restore immunity. Regardless of where stem cells come from, patients receiving these procedures still need lifelong treatment and may experience complex medical problems, including chronic infections.

In the latest study, researchers examined the safety and effectiveness of gene therapy in combination with low-dose chemotherapy in five sCID-X1 patients. The patients were between age 7 and 24, and were all experiencing worsening immune systems despite previous transplants from a parent. The scientists began by removing stem cells from the participants' bone marrow, then used a lentiviral vector to deliver a normal IL2RG gene to the cells. The cells were then inserted back into the patient after low-dose chemo, which helped the stem cells establish themselves and start producing new blood cells.

According to a press release, two of the patients who received the therapy showed significant improvements in immunity and clinical status, with one patient still showing improvement three years after therapy. The other patient, despite making improvements in immunity, unfortunately died of pre-existing, infection-induced lung damage two years after gene therapy, suggesting the importance of early treatment to prevent irrevocable organ damage.

The other three patients who received this type of therapy between 3 and 6 months ago are beginning to show some improvements in their immune function. The researchers are still monitoring the surviving patients and plan to continue doing so. They hope to be able to "determine the safety and effectiveness of lentiviral gene transfer as a treatment for children and adolescents with this immunodeficiency since transplant procedures aren't always effective."

Source: De Ravin SS, et al. Lentiviral hematopoietic stem cell gene therapy for older patients with X-linked severe combined immunodeficiency. NIH/national Institute of Allergy and Infectious Diseases. The American Society of Hematology 57th Annual Meeting. 2015.