Gene Therapy for Human Severe Combined Immunodeficiency Disease

Severe combined immunodeficiency (SCID) is a life-threatening disease, also known as the 'Boy in the Bubble' syndrome. Here's more.

Lymphocytes are white blood cells present in the immune system of vertebrates. T cells and B cells are the two types of lymphocytes. The immune system protects our body from infections. The T (thymus) cells are responsible for cell-mediated immunity, i.e., they boost other immune cells to oppose foreign substances.

B cells undertake the humoral immunity. They produce anti-bodies which fight with the antigens present in the humor (body fluid), hence the name humoral immunity. Defects in the T and B cells result in severe combined immunodeficiency syndrome. SCID is a genetic disorder. There are two major types of SCID.

XSCID

In this type of SCID, the gene that is present on the X chromosome, called IL2RG, is mutated.

ADA SCID

ADA (Adenosine Deaminase) is an important enzyme which helps in producing new DNA. In ADA SCID, the gene that encodes ADA is mutated.

SCID is detected in newborn babies. 1 among 80,000 live births are found to have SCID. However, babies suffering from SCID do not usually survive long. A SCID patient is susceptible to all kinds of infection, due to the improper functioning of the immune system.

What is Gene Therapy?

Gene therapy is a recent development in genetic and cell-based biotechnology in which genes are inserted in cells or tissues to deal with a genetic or hereditary disorder. The therapy has been successful in preventing and curing many genetic disorders. It includes replacement of the defective gene with a new gene.

Gene Therapy for Human SCID

In gene therapy for human SCID, the mutated gene present in the X chromosome (IL2RG), or the mutated gene that encodes ADA, is replaced by normal genes. The replacement makes the immune system work efficiently. In 1990, NIH (National Institutes of Health) was permitted to implement human gene therapy for the first time.

A four-year old girl, Ashanti DeSilva, suffering from ADA SCID was the first one to be treated. Some T cells were removed from her body and a normal copy of ADA gene was inserted into these T cells. These T cells were again injected into her body. Repeated treatments resulted in normalization of a number of T cells.

She had normal immunity, but continued receiving replacement of T cells. This experiment could not prove that gene therapy could completely cure ADA SCID, but it did prove that ADA SCID can be cured, if the proper gene was inserted into sufficient number of T cells.

In France, however, it was found that children treated for XSCID with gene therapy, developed leukemia. The method for insertion of corrected genes triggered an oncogene (cancer causing gene), which resulted in leukemia.

As a result of this, treatments for SCID were discontinued for a long period of time. Researches are being conducted to treat XSCID without triggering an oncogene. No cases of leukemia are seen in experiments carried out for the treatment of ADA SCID.

Other than gene therapy, bone marrow transplant and ‘Bubble Boy’ are some other treatments for SCID. Bone marrow transplant is the most effective. However, a proper ‘bone marrow match’ is necessary for transplantation. If a match is not found, SCID cannot be treated.

In Bubble boy treatment, the baby is kept in a bubble-like structure where it can be kept isolated from infections. Gene therapy, however, is a more efficient form of treatment in comparison to Bubble Boy. Moreover, as it is difficult to procure a ‘match’ in case of a bone marrow transplant, gene therapy can prove to be more beneficial.

So far, immune systems of 17 children suffering from either XSCID or ADA SCID have been restored by gene therapy. Although gene therapy of human severe combined immunodeficiency (SCID) has its limitations, it has proved to be an effective form of treatment.