The first gene therapy for children has just been approved in Europe
In a landmark moment for scientific research, the world’s first gene therapy treatment for children has been given the green light by the European Commission. It’s called Strimvelis, and it treats severe combined immunodeficiency (ADA-SCID) – a rare disorder that can be fatal in a very short space of time for those affected.
The disease leaves newborns with almost no defence against viruses and bacteria, and is closely linked to X-linked SCID or ‘bubble boy’ disease, so-called because of a young patient in the US who lived inside a protective plastic shield. What makes the new treatment special is that it’s the first time a commercial treatment has used genetic repair techniques to cure a disorder, and thanks to success in clinical trials, it’s now approved for marketing within Europe.
ADA-SCID is caused by a faulty gene inherited by both parents, and affects around 15 patients per year in Europe. The faulty gene stops the production of the adenosine deaminase (ADA) protein, which is required to produce white blood cells called lymphocytes. The disease often proves fatal before a child’s first birthday.
The disease is currently treated using a risky bone marrow transplant or lifelong and very expensive enzyme replacement therapy. In the case of Strimvelis, stem cells are removed from a patient’s bone marrow, corrected in a test tube to replace the faulty gene, and then reintroduced into the body.
“If you want to fix a disease for life, you need to put the gene in the stem cells,” paediatrician Maria-Grazia Roncarolo from Stanford University explained to Antonio Regalado at MIT Technology Review. Roncarolo was the leader of the team who originally tested the Strimvelis treatment.
“This is the start of a new chapter in the treatment of rare genetic diseases and we hope that this therapeutic approach could also be used to help patients with other rare diseases in the future,” said Martin Andrews, head of the Rare Disease Unit at GlaxoSmithKline (GSK), the company behind the treatment.
Gene therapy techniques are still so new that scientists and regulators are wary of introducing them too soon. This method of treatment has the potential to be hugely beneficial for medical science, but is essentially playing with the most fundamental building blocks of life. Swapping out genetic code is a lot more complicated than replacing a part in a car engine, though the principle is the same.
Of 18 children treated with Strimvelis in clinical trials, researchers found a 100 percent survival rate based on follow-up durations of between 2.3 and 13.4 years, which suggests that Strimvelis can indeed replace faulty genes with working copies without any adverse side effects – something that can’t be said for existing treatments.
“I would be hesitant to call it a cure,” GSK head of gene therapy development Sven Kili told MIT Technology Review. “Although there’s no reason to think it won’t last.”
The results of the clinical trials have been published in Blood.
Key points
•Survival was 100% for 18 patients with ADA-SCID treated with genetically modified CD34+ cells (2.3-13.4 years follow up, median 6.9 years).
•Long-term engraftment, immune reconstitution, and fewer severe infections in 15/18 patients were observed without leukemic transformation.
Abstract
Adenosine deaminase (ADA) deficiency is a rare, autosomal recessive systemic metabolic disease characterized by severe combined immunodeficiency (SCID). The treatment of choice for ADA-deficient SCID (ADA-SCID) is hematopoietic stem cell transplant (SCT) from a human leukocyte antigen (HLA)-matched sibling donor, although fewer than 25% of patients have such a donor available. Enzyme replacement therapy (ERT) partially and temporarily relieves immunodeficiency. We investigated the medium-term outcome of gene therapy (GT) in 18 patients with ADA-SCID for whom an HLA-identical family donor was not available; most were not responding well to ERT. Patients were treated with an autologous CD34+ enriched cell fraction that contained CD34+ cells transduced with a retroviral vector encoding the human ADA cDNA sequence (GSK2696273) as part of single-arm, open-label studies or compassionate use programs. Overall survival was 100% over 2.3 to 13.4 years (median: 6.9 years). Gene-modified cells were stably present in multiple lineages throughout follow up. GT resulted in a sustained reduction in the severe infection rate from 1.17 events per person-year to 0.17 events per person-year (n=17, Patient 1 data not available). Immune reconstitution was demonstrated by normalization of T cell subsets (CD3+, CD4+, and CD8+), evidence of thymopoiesis, and sustained T cell proliferative capacity. B cell function was evidenced by immunoglobulin production, decreased intravenous immunoglobulin use, and antibody response after vaccination. All 18 patients reported infections as adverse events; infections of respiratory and gastrointestinal tracts were reported most frequently. No events indicative of leukemic transformation were reported. Trial details are registered at www.clinicaltrials.gov as #NCT00598481.