Severe combined immunodeficiency (SCID), or "Boy in the Bubble" Syndrome, is a genetic disorder in which both "arms" (B cells and T cells) of the adaptive immune system are affected, due to a defect in one of several possible genes. Wisconsin and Massachusetts (as of February 1, 2009) screen newborns for SCID.
Severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA) is a fatal disorder of purine metabolism and immunodeficiency. ADA deficiency accounts for about 15% of all cases of severe combined immunodeficiency (SCID).
ADA irreversibly deaminates adenosine (left), converting it to the related nucleoside inosine (right) by the removal of an amino group (observe missing nitrogen in upper left). Image source: Wikipedia, public domain.
In ADA deficiency, there is an accumulation of deoxyadenosine, which causes an increase in S-adenosylhomocysteine; both substances are toxic to immature lymphocytes, which thus fail to mature. As a result, the immune system is severely compromised or completely lacking.
A multi-center study investigated the long-term outcome of gene therapy for SCID due to ADA deficiency.
How did they do it?
1. Enzyme-replacement therapy was given before the gene therapy.
2. CD34+ bone marrow cells were transduced with a retroviral vector containing the ADA gene.
3. Nonmyeloablative conditioning with busulfan.
4. The autologous CD34+ bone marrow cells transduced with a retroviral vector were infused.
All patients were alive after a follow-up of 4 years. Transduced hematopoietic stem cells have stably engrafted and differentiated into myeloid cells containing ADA.
The authors concluded that gene therapy, combined with reduced-intensity conditioning, was a safe and effective treatment for SCID in patients with ADA deficiency.
Severe combined immunodeficiency (SCID) - 4 groups according to T/B/NK cells (click to enlarge the image).
Gene Therapy for Immunodeficiency Due to Adenosine Deaminase Deficiency. Alessandro Aiuti et al. NEJM, Volume 360:447-458 January 29, 2009 Number 5.