The first successful gene therapy of a baby with severe combined immune deficiency (SCID)
Severe Combined Immunodeficiency (SCID) caused by the deficiency of an enzyme known as Adenosine deaminase (ADA) is a lethal disease caused by unavoidable fatal infections. The disease is also known as “bubble baby“ because such newborns had to be protected from infections and locked inside closed bubbles.
The only potential cure could be provided by successful gene therapy by insertion of the gene responsible for synthesis of ADA inside multi-potent stem cells that are responsible for development of immune system cells. Unfortunately, all prior attempts for gene therapy of such SCID patients failed.
In 2002, a new ADA-deficient SCID newborn was presented to Prof. Slavin. One child of the same family died of recurrent infections before being diagnosed. A sister with ADA-deficient SCID that was born later was cured by Slavin following successful allogeneic stem cell transplantation using normal cord-blood stem cells cryopreserved following delivery of a normal brother (picture shown on the left). No donor was available for the new case of SCID so Slavin decided to try and cure the baby using gene therapy using ADA-vector provided by Italian colleagues. Considering prior failures to cure similar SCID patients by several international teams using a similar ADA vector, Slavin decided to apply a different strategy for transplantation of patient’s own ADA-transduced cord blood and bone marrow stem cells.
The new SCID baby girl shown in the picture, Tasnin, was cured in 2002 using successful gene therapy. This used the vector carrying the missing ADA gene that was introduced into her ADA-deficient hematopoietic stem cells.
First, the SCID baby was conditioned using harmless non-myeloablative conditioning to create a “niche” for more effective homeostatic proliferation of genetically transduced autologous stem cells. Then, the patient’s genetically transduced stem cells were infused. Indeed, rapid engraftment and differentiation of genetically engineered stem cells resulted in rapid immune reconstitution of Tasnin following an uneventful recovery and no need for any additional treatment since then.
Tasnin is the first successful patient treated with gene therapy for ADA-deficient SCID. This was based on Slavin’s method to ensure consistent engraftment and normal multi-lineage differentiation of genetically engineered stem cells.
The photos show Tasnin on the right side with her sister and with her mother on the right, fully recovered 4 years after successful gene therapy. On the left side is Salsabil (Tasnin’s sister) who was also born with the same disease and was cured by allogeneic cord blood stem cell transplantation. The patient is alive and well and remains free of any medical problems since 2002.