Abstract:
Introduction. About 1 in 500,000 people are born with severe combined immunodeficiency (SCID).
The adenosine deaminase variant is a fatal inborn error of purine metabolism. Accumulation of
adenosine and deoxyadenosine leads to inhibition of DNA synthesis and repair, as well as
abnormalities of thymocyte development, vital in an evolving immune system. Patients with ADASCID often die prematurely from infection. Currently, treatments include PEGylated enzyme therapy
and allogenic stem cell transplantation from a matching HLA donor, however their success is variable.
These treatments are also temporary, complicated, and carry a high risk of death. Gene therapy using
a Lentiviral vector shows promising results for treatment of SCID.
Aim of study. Evaluating the current possibilities and post-treatment outcomes of implementing gene
therapy for ADA-SCID.
Methods and materials. The study includes a specialized literature review of research/clinical trials
published in PubMed, NIH, and the New England journal of medicine. Key words include “SCID”
“Gene therapy”. Information contains results of studies done in Asia, Europe, and the United States
evaluating efficacy, safety and long-standing outcomes of gene therapy for ADA-SCID with viral
vectors.
Results. Comparing patients treated with PEGylated enzyme therapy and stem cell transplant, patients
enrolled in clinical trials treated with Gene therapy (GT) demonstrated immune reconstitution, and
event free survival. Treatment involves obtaining stem cells from the patient’s bone marrow. Once
isolated the therapeutic genetic material is implemented into a lentiviral vector (LVV). The LVV can
integrate the RNA into the nuclear DNA of the host target cells. The patients are given an injection of
Busulfan to decrease their defective cells. The new cells are then transfused back to the patient,
effectively coding for the deficient ADA gene leading to production of the enzyme. Results show
decreased toxic metabolites and immune reconstitution. Although survival rates in patients treated with
GT are 100%, clinical trials remain highly limited and commercial GT is not currently available.
Conclusion. Genetic therapy using Lentiviral vectors is an effective and safe treatment for patients
with ADA-SCID. Long term outcomes show minimal complications and complete cure of the disease.
The therapy remains limited due to resources and high costs.
