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

This is a study of extraordinary relevance and high methodological quality. It demonstrates that gene therapy with a lentiviral vector for adenosine deaminase deficiency (ADA-SCID) is effective (95% of patients) and safe, with low toxicity compared to the current alternative, hematopoietic transplantation. The stability of the vector copy number (VCN) in white blood cells suggests disease correction in stem cells, a key marker of cure. This is the largest published series with extended follow-up (more than five years), requiring, in most cases, a single infusion.

It confirms and expands previous short-term results, showing sustained T, B, and NK cell reconstitution for more than seven years, immunoglobulin independence in 98% of patients, and good vaccine responses, also allowing the discontinuation of anti-infective prophylaxis.

In terms of safety, it clearly improves on treatment with gamma-retroviral vectors. Lentiviral vectors are gaining ground precisely because of their lower risk of insertional mutagenesis, which leads to the development of leukemia in patients with older gamma-retroviral vectors.

The use of cryopreserved products, in addition to fresh ones, allows for centralized manufacturing and infusion at other centers, avoiding travel to the few institutions with production capacity and compliance with regulatory requirements.

Another key advantage is that, if gene therapy should exceptionally fail, the patient is still a candidate for an allogeneic transplant; conversely, a prior transplant precludes access to gene therapy.

The only limitations are three, and they are not exclusive to this therapy, but to gene therapies in general: first, the need for long-term follow-up for every patient who has received cell therapy. Next, the cost and logistical complexity of the treatment (in terms of manufacturing and financing) in a strained healthcare system. Finally, the latency to immune reconstitution of the patient (six to twelve months), the period during which the risk of infection and daily life restrictions persist. It is imperative to develop strategies to accelerate this recovery.

My conclusion is that this is a highly relevant study in a disease as rare as severe combined immunodeficiencies (the so-called "bubble boy" syndrome). This study consolidates lentiviral gene therapy (via single infusion) as a priority and safe curative option for ADA-SCID, with a direct impact on treatment guidelines. Regulatory agencies should prioritize its implementation where feasible, ensuring cost sustainability and long-term safety.