Gene therapy offers treatment to children without immune system, suggests study

The new therapy could ultimately remove the need for bone marrow transplants in children without an immune system.

Gene therapy offers treatment to children without immune system, suggests study

Researchers have made a “significant breakthrough” with a gene therapy that treats children with a form of severe combined immunodeficiency which leaves them without an immune system.

Severe combined immunodeficiency due to adenosine deaminase deficiency, also known as ADA-SCID, is a rare, life-threatening disease that prevents children from living a normal life.

It is caused by mutations in the gene that creates the enzyme adenosine deaminase, which is essential to a functioning immune system.

Children with the condition have no immune system, and the condition can be fatal within the first two years of life if it is left untreated.

In a new study published in the New England Journal of Medicine, co-lead authors Professor Donald Kohn, University of California, Los Angeles (UCLA), and Dr Claire Booth, Great Ormond Street Hospital (GOSH) reported the two- to three-year outcomes of 50 children.

They were treated in clinical trials with an experimental stem cell gene therapy for ADA-SCID between 2012 and 2017.

Adrian Thrasher, professor of paediatric immunology at GOSH and Wellcome Principal Research Fellow, said: “We started gene therapy at GOSH around 20 years ago and now have refined the process to offer a potential cure for children born with this debilitating condition.

“Over 200 patients with various genetic conditions across the world have now been treated with this type of gene therapy – this is another very significant breakthrough.”

The standard treatment for the condition involves once or twice weekly injections of the ADA enzyme until a bone marrow donor – usually a close family member – can be found.

If a matched donor is not available, patients require lifelong ADA injections, as well as preventative medicines.

Researchers say that if approved, gene therapy would be a welcome new treatment option for ADA-SCID as it is a one-time procedure that has the potential to provide life-long results.

Two to three years after the treatment, all of the 50 children treated with the new gene therapy at GOSH, UCLA Mattel Children’s Hospital and the National Institutes of Health (NIH) are alive and well.

Of these, 48 are no longer showing symptoms of ADA-SCID, but they will be monitored for life.

In the two cases in which treatment wasn’t successful, both children were able to return to current standard treatments, with one eventually receiving a bone marrow transplant.

Researchers report no serious side effects so far, with generally mild or moderate complications experienced from the necessary preparation for the gene therapy.

Dr Booth, Mahboubian associate professor in gene therapy and GOSH consultant in paediatric immunology and gene therapy, said: “If approved in the future, this treatment could be standard for ADA-SCID, and potentially many other genetic conditions, removing the need to find a matched-donor for bone marrow transplant and the toxic side effects often associated with that treatment.

“We need and want guidelines to change so we can start offering this potential cure to children and provide it as a first-choice treatment – this research could set those wheels in motion.”

In earlier trials of gamma-retroviral gene therapy for other similar diseases, serious side effects including leukaemia have been seen in some patients.

But the researchers say lentiviral gene therapy technology has advanced significantly and offers the potential to improve the safety and efficacy profile of this treatment option for patients.

The therapy described in the paper involves first removing some of the patient’s blood-forming stem cells, which create all types of blood and immune cells.

Next, a viral vector is used to deliver a new copy of the ADA gene into the DNA of the patient’s cells.

These corrected stem cells are then returned to the patient where, once engrafted, they go on to produce a seemingly continual supply of healthy immune cells capable of fighting infection.

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