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

This is a long-term follow-up article (minimum five years) of a series of patients (one cohort from California and another from the United Kingdom). It provides evidence of the long-term safety of gene therapy and is therefore highly relevant. ADA-SCID was the first immunodeficiency described where gene therapy was established. This work provides data on the high long-term safety and efficacy of this type of approach and is applicable to many other genetic diseases.

Current treatment is based on bone marrow transplantation from a haploidentical (HLA-identical) donor and the use of pegylated ADA enzyme replacement. This treatment does not reach the levels demonstrated in [this study] in the presented series, with 100% survival and 95% freedom from clinical events after a long follow-up period. They show how immune reconstitution is excellent, even with a good response to vaccines and the discontinuation of immunoglobulin replacement therapy. Patients undergo myeloablative treatment similar to other bone marrow transplants, but at much lower doses and, therefore, with fewer post-treatment problems. Furthermore, significantly, the patient's own cells for gene therapy were just as effective fresh as frozen, which facilitates manipulation with lentiviruses, as is the case at other facilities without the need for patient travel.

I see no major limitations, except for one aspect. Most of the patients in the California series were diagnosed with newborn screening using TREC (T-cell receptor excision circle) amplification, while in the United Kingdom they were diagnosed after birth. Although no differences were seen in post-transplant outcomes, there is no doubt that newborn screening allows these patients to be identified at birth and to establish targeted gene therapy as planned.