Gene therapy success in Severe Combined Immunodeficiency Disorder

Rare mutations in the Interleukin 2 receptor gene (IL2RG) causes nearly half of all cases of X-linked severe combined immunodeficiency (SCID-X1), a condition that impairs the production of immune cells, including T cells, and leaves a person vulnerable to even the most benign infections.

SCID can be treated with hematopoietic stem cell transplantation of a matching donor's cells, but donors are difficult to find and the treatment can come with side effects. Another treatment option is gene therapy, in which the patient's defective immune stem cells are extracted and genetically engineered to form a new population of functional T cells.

A group of researchers from the United Kingdom and Saudi Arabia treated 10 children four years of age and younger by gene therapy using a conventional gammaretroviral vector, and published their results in Science Translational Medicine.

After an average of 6.5 years, all patients were alive and their T cells were restored to varying degrees. The most important factors determining how well T cells were restored were cell dose, patient age and clinical conditions. The treatment restored immune function in all of the patients but one, who developed leukaemia. The oldest child, at four years of age when treated, developed modest immunity compared to those treated in the first year of life.

Antibody secreting B cells reached normal levels, however, the systemic humoral immunity only partially recovered. Several patients were able to discontinue immunoglobulin replacement treatment.

The team suggests further research on how to enhance B cell reconstruction and limiting mutagenesis related to the vector used in gene therapy could further enhance the treatment as a viable option in conjunction with stem cell transplantation.

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