A recent study from researchers at the UCLA, Great Ormond Street Hospital for Children London, et al, has proven the efficacy of an autologous ex vivo lentiviral gene therapy in treating patients with ADA - SCID (severe combined immunodeficiency due to adenosine deaminase deficiency).

Lentiviral vectors in gene therapy is a method by which genes can be inserted, deleted or modified in tissues using lentivirus.

ADA-SCID is a rare immune disorder that is caused by the inherited deficiency of adenosine deaminase.The resulting severe combined immunodeficiency leaves patients unable to fight off most types of infections. Without treatment, patients rarely survive past the age of two. The annual incidence of ADA deficiency is estimated to be between 1/200,000 and 1/1,000,000 live births.

According to the study, 50 patients were treated with an investigational gene therapy composed of hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with a self-inactivating lentiviral vector encoding human ADA.

Of the total patient population 30 were located in the US and 20 in the UK. An overall survival of 100% was achieved up to 24 and 36 months as part of the study in both patient groups.

The study also reports the timewise percentage of event free survival.

Event free survival implies survival in the absence of enzyme-replacement therapy or rescue allogeneic hematopoietic stem-cell transplantation to treat the patients. The survival percentage was 97% and 95% respectively for the US and the UK studies at 24 months and 95% for the UK study at 36 months.

Engraftment of the genetically modified HSPCs was also shown to persist in a remarkable majority of the patients involved in both the US and the UK studies. The study reads,“Patients had sustained metabolic detoxification and normalization of ADA activity levels.”

The study adds that immune reconstitution was also robust in the patients and that 100% patients in the UK discontinued immunoglobulin replacement therapy by 36 months while the same parameters were 90% and 24 months respectively for the US study.

The study states that there was no evidence of monoclonal expansion, leukoproliferative complications, or emergence of replication-competent lentivirus, and that no events of autoimmunity or graft-versus-host disease occurred. Most adverse events which were observed as part of the study were of low grade.