Great Ormond Street hoping to license gene therapy for ‘bubble baby’ syndrome | Medical research

When Great Ormond Street Hospital (God) publish the results of his gene therapy trial for “bubble baby” syndrome was hailed as a medical breakthrough. The treatment has a more than 95% success rate for treating a life-threatening disease in which children have no immune system. But less than a year later, the therapy was abandoned by the pharmaceutical company that had planned to bring it to market.

Now Gosh is taking the unprecedented step of trying to license the therapy itself on a non-profit and non-industry basis to make it more widely available to babies and children around the world.

“We developed the treatments, saw the amazing results in the trial and then hit this hurdle,” said Prof Claire Booth from Gosh and University College London, who was the trial’s principal investigator. “We are seeing more and more companies withdrawing from the field. So we had to find a way to deliver it to patients.”

The move comes amid concerns about the affordability of gene therapies, which could leave them out of reach for many patients. Medicine for spinal muscular atrophy Zolgensma is priced at £1.6mwhile the National Institute for Health and Care Excellence recently refused to approve NHS funding for Casgevya recently licensed gene-editing therapy for sickle cell disease.

But, Booth said, these treatments “literally don’t cost £1 million” and could cost a tenth of that under the approach Ghosh hopes to pioneer.

The hospital plans to submit an application next year to the UK regulator, the Medicines and Healthcare Products Regulatory Agency, to treat ADA-SCID, a devastating genetic disorder that affects about one in 500,000 people, which equates to one in three people born in England each year. Children with the disease have no immune system and the condition can be fatal within the first two years of life if left untreated. Everyday activities like going to school or playing with friends can lead to a dangerous infection.

Standard treatment involves weekly injections of an enzyme or a bone marrow transplant if a donor can be found. Both options require lifelong treatment and carry the risk of complications.

The gene therapy approach is a one-time treatment in which the stem cells are harvested, genetically reprogrammed, and reintroduced to the patient. “The cells go back into the patient, go into the bone marrow, and then develop a whole new working immune system that should sustain them for the rest of their lives,” Booth said.

Currently, the treatment can be offered to patients on a compassionate use basis, but “it’s not a sustainable way to do it,” Booth said. A license can make it a standard, approved treatment.

Booth and his colleagues have received £350,000 from medical charity LifeArc and Gosh’s charity arm to prepare an application to regulators. The hope is that this will pave the way for a similar approach to bringing other gene therapies to market.

Dr Catriona Crombie, Head of Rare Diseases at LifeArc, said: “It is unacceptable to us that there are proven treatments not reaching patients due to commercial challenges, and we are determined to drive change. Unfortunately, we know that this is not the only gene therapy drug for a rare disease that is being abandoned or not developed for commercial reasons.

“We are extremely pleased to be partnering with Gosh to see if this model can lay the groundwork for a whole new way of giving more people access to life-changing treatments. If successful, we hope this could be a proof of concept that will allow other gene therapies to be made available for rare genetic diseases.

“Let’s give these kids a chance”

The first signs that something was wrong weren’t alarming: baby Sarah had diaper rash, thrush and wasn’t putting up. “I tried to stay calm, thinking that every child has these things,” recalls her mother, Maria-Louise Prioteasa. But when, at one month, Sarah was still losing weight and developed a chest infection, she was admitted to hospital for testing. A blood test reveals that Sarah has ADA-SCID, sometimes called “bubble boy syndrome,” which means she has no functioning immune system.

The standard treatment for the condition is a bone marrow transplant, but there was no matching donor on the registry and neither Priotease nor Sarah’s father were compatible. “I know the feeling as a parent when you think everything is gone,” says Prioteasa. But at that point, the family learned of a gene therapy trial at Gosh that doctors hoped would provide a cure. “We signed the papers because it was the only option at the time,” says Prioteasa.

At just six months old, Sarah became one of the first babies in the world to receive the therapy, which involved removing cells from her bone marrow, genetically reprogramming them in the laboratory and reintroducing them into her body. The treatment was successful and after six months, Sarah was able to reduce her immune meds and was allowed to go out for the first time since her diagnosis without a plastic cover over her stroller. “I would cross the road if someone was coming towards me,” says Prioteasa.

Sarah recently turned eight and is a happy, healthy and active child. “She’s doing really well,” says Prioteasa. “She went to daycare, she goes to school, I’m not afraid that she won’t get infected in the winter. I let her be like everyone else. I owe [Gosh] her life.”

However, other families she met through patient forums are still living under the shadow of the disease. “I see it’s gone in other places. These kids stay in the house, you can’t have life as a child and life as a parent,” she says. “There are many people who wait years to get treatment. Not fair. Let’s give these kids a chance.”