Reacción a "Gene therapy is effective long-term in children with a serious rare disease"

I find this interesting. It's true that the authors had previously published a study with 50 patients, and now they've increased the number to 62 and extended the study period. They had already demonstrated the efficacy of gene therapy.

A deficiency in the enzyme aminodeaminase (ADA) causes severe combined immunodeficiency, affecting both T and B lymphocytes. This is due to the toxic accumulation of compounds that should be modified by this enzyme, and when it's absent or defective, it can't perform its function.

Children with this defect are "bubble babies," as they can only survive in sterile spaces and often die of infections at an early age.

The solution to their problem is very complex:

1. Bone marrow transplant from a healthy person. In this case, the idea is to administer cells that carry the correct gene. It is a procedure that carries risks, requires immunosuppressive treatment, and is at risk of infection, as well as the possibility of graft-versus-host disease (GVHD) as it is a transplant from another individual (allogeneic).
2. Continuous administration of the ADA enzyme is not always effective, and adequate levels are not achieved for a fully effective immune system.
3. By using modified viruses, the gene that codes for this protein is introduced. The patient's own cells are used, modified ex vivo, and reintroduced. This is what these authors have done.

Gene therapy has been attempted for many years, initially with adenoviruses or lenti-adenovirus hybrids, but some problems have been seen, such as cases of leukemia due to integration into DNA, activating oncogenes.

These researchers have developed gene therapy with a self-inactivating lentiviral vector, which contains a shortened elongation factor promoter that directs the expression of the ADA transgene.

They performed gene therapy on 62 patients, with a long follow-up period (some more than seven years). They found good acceptance of the treatment, and no serious side effects were detected, nor were any development of leukemias.

The vector copies, their maintenance over time, immune reconstitution, and side effects were systematically analyzed. It is a very comprehensive study.

The implications are that this type of viral vector could be used for this gene therapy for ADA deficiency, and for others in the future. Given its few side effects and the fact that no leukemias were detected, it appears to be a fairly safe therapy compared to previous therapies using adenovirus or gamma lentivirus.

[Regarding possible limitations] They studied two cohorts, one in the US and one in England, which increases the robustness of the study, as it was conducted in two locations. There are also differences regarding the cells used as the starting material, with bone marrow being the majority in the American cohort and peripheral blood stem cells in the English cohort. However, no significant differences were observed between the two cohorts.

In collaboration with other groups, it would have been desirable to have a direct comparison with patients who have received other types of gene therapy and to compare long-term side effects, maintenance, and reconstitution of the immune system.