鈥淲e nearly lost him twice,鈥� says聽Kelly Gillion of her son Zeus, who was diagnosed with the potentially fatal condition ADA-SCID in the first weeks of his life.
Until now the only commercial treatment for the condition has been a bone marrow transplant, and many die before a donor is found. But last week, a gene therapy to treat it was rubber-stamped for approval by a committee of the European Medicines Agency, potentially giving all patients in Europe access to a treatment that enables them to build lifelong immune systems with the help of transplanted genes.
The outcome has been hailed as a triumph for gene therapy after decades of high-profile setbacks.
Advertisement
鈥淚t鈥檚 an amazing moment and an absolute landmark for gene therapy,鈥� says Susan Walsh, director of PID UK, a charity representing parents and children with inherited immunodeficiency diseases. 鈥淭he great thing is that an advance in one area improves prospects for other conditions,鈥� she says.
Children with severe combined immunodeficiency (SCID) don鈥檛 have a working immune system and even routine infections can be聽fatal. The need to keep babies with SCID isolated has led it to be dubbed 鈥渂ubble baby鈥� disease. In ADA-SCID, children have defective copies of the gene that makes adenosine deaminase (ADA), an enzyme indispensable to the immune system. Without it, toxic debris builds up in white blood cells and kills them before they can mature.
Zeus was lucky enough to find a bone marrow donor (see 鈥淕etting out of the bubble鈥�, below), but many children die as babies waiting for one.
An alternative treatment called Strimvelis should now become available. It has been developed by teams at the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy, and pharmaceutical giant GlaxoSmithKline (GSK) and permanently alters DNA within a聽patient鈥檚 cells.
The procedure involves extracting the bone marrow stem cells that regenerate the immune system and infecting them with a聽harmless virus that uploads a correct copy of the gene for ADA. The altered cells are injected back into the patient where, unlike their native counterparts, they are聽able to generate a healthy immune system.
To win approval, GSK submitted data on 22 patients, a聽mix of boys and girls treated in聽Italy at an average age of 18聽months. Full details are being withheld for journal publication, but the company says that they were a success. 鈥淥f the patients in the trial, we鈥檝e seen 100 per cent survival,鈥� says Sven Kili, head of gene therapy development at GSK. 鈥淭he first patient is now 13聽years post-treatment, and the median over all the patients is seven years survival so far.鈥�
Although this is the first time this technique has won approval, for more than 20 years, children with ADA-SCID have been treated with a similar procedure on a trial basis at Great Ormond Street Hospital in London and the Necker Hospital in Paris. Cases of leukaemia in 2002 in four of the treated French children led to suspension of that trial until 2005.
鈥淚鈥檓 hesitant to call it a cure.聽But we have no reason to suspect that it won鈥檛 be indefinite鈥�
The virus used in Strimvelis is the same as the one that gave rise to the leukaemia but GSK is monitoring for complications.
The first and only other gene therapy approval was Glybera in 2012, a gene product injected into the muscles of people with lipoprotein lipase deficiency. It聽makes the enzyme they lack聽鈥� which breaks down fatty waste.
The ADA-SCID treatment is the first that alters the DNA in stem cells taken out of the body and in the future cells they produce. 鈥淭he聽gene we insert is assimilated completely into the genome,鈥� Kili says. This聽should mean the effect is long-lasting, even permanent.
鈥淲e鈥檙e aiming for lifelong outcomes, so I鈥檓 hesitant to call聽it聽a cure,鈥� says Kili. 鈥淏ut the stem cells we鈥檝e altered go on to聽replicate so we have no reason to suspect that it won鈥檛 be indefinite,鈥� he says.
Doctors at the Milan institute have also used the technique to treat 20 children with a fatal, nerve-destroying inherited disease called metachromatic leukodystrophy. In future, the team hopes to try it聽on an inherited condition called beta thalassaemia and even more common conditions such as rheumatoid arthritis.
鈥淲e鈥檝e seen the huge impact gene therapy can have on children鈥檚 lives,鈥� says Bobby Gaspar of Great Ormond Street. 鈥淎pproval of a licensed gene therapy medicine for SCID is a very positive step and shows that gene therapy can become a standardised medicine.鈥�
Getting out of the bubble
鈥淲e couldn鈥檛 believe it when we were told he had pretty much no immune system,鈥� says Kelly Gillion of son Zeus. At 10 weeks he was diagnosed with a rare disease called ADA-SCID, caused by a deficiency of the adenosine deaminase (ADA) enzyme.
He was given synthetically produced ADA every week, which kept him alive while doctors searched for a bone marrow donor. 鈥淥ur lives were turned upside down,鈥� says Gillion. 鈥淣o one could come round and see us if they had colds or coughs,鈥� she says. 鈥淏asically, our family was in lockdown for a whole year.鈥�
Then, through the Anthony Nolan charity, a matching bone marrow donor was found in Germany, placing Zeus among the lucky 60 or 70 per cent of patients who can be helped this way.
It鈥檚 not a pleasant treatment though. First the original bone marrow cells have to be wiped out using chemotherapy before they are replaced. 鈥淭hat was awful,鈥� says Gillion. 鈥淚t takes so long for the immune system to grow, he was still in isolation till he was 3.鈥�
Now, Zeus is 6, at school and healthy, but Gillion says she knows of others who are not so lucky. Gillion is delighted that gene therapy will soon become available. 鈥淚t鈥檚 great for the future of ADA-SCID,鈥� she says.