New Vector for Treating X-linked Severe Combined Immunodeficiency

X-linked severe combined immunodeficiency (SCID-X1) is an inherited, life-threatening condition which affects approximately 1 in 50,000 to 100,000 newborns, almost all of which are boys. SCID-X1 rarely affects girls because the mother must be a carrier for the mutation, and the father must have SCID-X1. SCID-X1 is caused by a mutation in the IL2RG gene. This mutation essentially prevents lymphocytes from properly maturing and functioning. Ultimately, in SCID-X1, the immune system is drastically weakened, resulting in chronic infections and probable death.

SCID-X1 is ideally treated via a transplantation of blood-forming stem cells and gene therapy; however, some patients do not have a matched bone marrow donor. In the case of lacking a suitable donor, "doctors remove stem cells from the patient's bone marrow." Then, using a Maloney murine leukemia virus-based-gamma-retrovirus vector, a corrected gene is inserted into the cells, and the cells are then returned to the patient. This method has worked in restoring immune function; however, after two to five years from receiving the treatment, one-quarter of the patients developed leukemia. This vector "may activate genes that control cell growth," unluckily leading to leukemia.

Currently, a study is being conducted to evaluate the outcome of using an engineered self-inactivating gamma-retrovirus vector to treat SCID-X1. The study consists of nine boys with SCID-X1 who received gene therapy using this vector form. This treatment has produced positive results in seven of the nine boys who "developed functional T cells at levels comparable to those seen in previous studies and have remained healthy for one to three years after treatment." The results from analyzing the boys' T cells indicate that the self-inactivating vector "causes fewer genomic changes that could be linked to leukemia." One of the boys who did not respond well to the treatment passed away from a previously existing viral infection, and the other received a stem cell transplant. The boys who did respond to the treatment will be regularly monitored for the development of leukemia.

Although the condition appears fairly rare with only 1 out of 50,000-100,000 boys being affected, this number means there are anywhere from 3,161 to 6,322 boys suffering from this condition in the United States. Knowing that 3,000-6000 boys may have to be placed in a bubble to prevent infections is very saddening; however, the development of the self-inactivating vector can ultimately strengthen the boys' immune systems. This will allow them to live life the way a young boy should while also reducing and potentially eliminating the increased risk of developing leukemia from the treatment.

This article reopened my eyes to the complexity of the human body almost leaving me dumbfounded. While it may seem like the human species has everything figured out, there is so much information to be learned.

Article: http://www.niaid.nih.gov/news/newsreleases/2014/Pages/SCIDtherapy.aspx
Related Article: http://www.nejm.org/doi/full/10.1056/NEJMoa1404588#t=articleResults