Scientists in a laboratory at the heart of London’s most famous children’s hospital are hoping they can make treatment for rare diseases cheaper and quicker to access, after five years of pioneering new medicine.
Babies born without a functioning immune system and children with aggressive blood cancers have been successfully treated using gene therapy thanks to research carried out at the Zayed Centre for Research into Rare Disease, which is part of Great Ormond Street Hospital (Gosh).
Zayed Centre for Research
The highly complex and sensitive therapy involves injecting a working gene into the patient's body, to correct the faulty one. Some diseases can be treated with just one injection. In addition to the laboratory, the centre has a facility to make its own gene therapies for patients, and treats hundreds of children a day with a range of conditions in a ward within the same building.
But the doctors face a challenge: the diseases they cure are so rare that no pharmaceutical company is willing make the drugs once they have been developed and tested at the centre.
Prof Claire Booth, a world expert in gene therapy who leads clinical research at the centre, hopes to solve this by obtaining a market authorisation licence. This would allow the hospital to make the treatments more widely available on a non-commercial basis.
“We've seen in the past few years that commercial partners are less interested in rare disease gene therapies. It's just not commercially feasible for them, and we wonder whether we are able to fill that gap,” she told The National.
Their first case study for this pilot project will be for a treatment for ADA-SCID, an inherited immune system disorder, which was developed at the Zayed Centre for Research, and shown to be 95 per cent effective in clinical trials. A pharmaceutical company had initially planned to bring the drug to the market but pulled out a year later.
The mother of an eight-year-old patient who was successfully treated for ADA-SCID by the clinical trial when she was a baby, said she hoped more children would be able to access gene therapy.
“We have always felt quite lucky that [our child] got the treatment when she did, but it was only through the research programme that she got it. To think that we now know the gene therapy can work and families still can’t get it seems senseless," she said in a statement to the UK charity LifeArc in April.
If Prof Booth and her team succeed, the hospital would have achieved a first in NHS history. “It would be the first time that an NHS trust has held a licence for an advanced therapy,” she said of the initiative, which is supported by LifeArc and Gosh's charity arm.
Five years of innovation
The centre celebrates its fifth anniversary this month. The laboratory is the largest in Europe, and patients or visitors can watch its scientists at work from the street before they go into the building. Its outpatient ward has had 17,000 appointments in the last year alone.
It was built partly with a £60 million donation from Sheikha Fatima bint Mubarak, Mother of the Nation, and is a partnership between Great Ormond Street Hospital, University College London and Great Ormond Street Hospital Children's Charity.
Another major breakthrough at the centre has been the treatment for a rare and “incurable” form of leukaemia, using gene therapy. Doctors took T-cells, a type of white blood cell that fights infections, from a healthy patient and modified them to into CAR T-cells that attack and kill the cancerous T-cells.
Alyssa, a 15-year-old patient from Leicester, was the first to receive the treatment in a clinical trial in March 2022. She was in remission 28 days after her first bone marrow transplant at Gosh, and has remained cancer-free since, though she continues to have regular checks.
“If you are able to stop children having the impact of chemotherapy in their treatment for cancer, and replace that with the same type of immune response that you might have if you're treating a cold, that's a better and a kinder treatment,” said Sarah Bissell, deputy director for relationship fundraising at Gosh.
Prof Booth hopes to see the new technologies in gene editing being used to treat a wider variety of patients with rare diseases in the next five years. “We’re really at the point of seeing those exciting technologies moving forwards into clinical trials for patients with rare genetic diseases,” she said.
Doctors are also looking forward to opportunities afforded by the centre’s pioneering use of laboratory-grown organs, known as organoids. For years researchers around the world have struggled to control their growth – which made them less accurate for research purposes.
Last year, the Zayed Centre for Research announced it had made a breakthrough using 3D printing to stop the uncontrolled growth. “Going forward, we will have more accurate treatments that we're able to develop, but it will also mean things like we will need to test treatments less on animals” Ms Bissell said.
Researchers are currently looking at how a heart develops in the early stages of a baby’s growth. “Understanding that better will enable treatments for congenital heart diseases and cardiovascular disorders in children,” Ms Bissell added.
The centre has introduced new approaches to allow doctors to diagnose epilepsy faster and with greater accuracy, potentially improving outcomes for young patients.
The “synergy” between the centre’s research and treating patients at Great Ormond Street Hospital is at the heart of the building’s philosophy, Prof Booth explained. Patients on clinical trials are treated with drugs that have been developed at the lab, where all the pre-clinical research is done. “The drugs are manufactured here, and we treat the patients here,” she said.
The centre has its own facility to make gene therapy products – known as a good manufacturing practice suite (GMP) – which was licensed to do so by the Medicines and Heathcare Products Regulatory Authority last year. Since then, the facility has made viral vectors – viruses that carry and transmit the corrected gene into the body – that are required for gene therapy, in partnership with commercial company Virocell Biologics.
A market authorisation licence would allow the hospital to work without the need for a commercial company. “This will mean that we can take drugs, develop them, deliver cures to children, and that is a groundbreaking opportunity for children with rare diseases around the world,” said Ms Bissell.
Louise Parkes, chief executive of Gosh Charity, said of the centre's fifth anniversary: “It is incredible how many groundbreaking advances have been made by our experts in that time, from gene-editing therapies to rapid genome sequencing and so much more.
“For many children with rare diseases, research is their only hope of treatment or a cure. At Gosh Charity we stop at nothing to help give seriously ill children the best chance possible and a huge part of that is funding groundbreaking research to offer hope for countless young people around the world.”
International impact
These contributions are not just limited to treating patients in the UK. "Some of the research that's happening here is breakthroughs that the world is looking at,” Ms Bissell said.
Treatments that were pioneered at the centre are now being worked on in the US and in China, she said. “The Zayed Centre is fuelling research into childhood diseases around the world."
The work at the centre is also feeding into the UAE’s own plans to develop a genomics programme and become a regional hub for health care. Over the past five years, Emirati researchers and doctors have been trained at Gosh before going back to the UAE.
Among them is Dr Mohammed Al Ameri, a former researcher in genomics and childhood leukaemias at the Zayed Centre for Research, who is now a genome lead at the Abu Dhabi Health Authority. "Because of the kinds of rare diseases that we've been seeing here in the Zayed Centre for Research and also back in the UAE, we needed a solution. The solution to these kinds of diseases is gene therapy, a one shot that will solve the issue," he told The National.
“The vision that I see for the UAE is that we become a hub for genomics, at least for the region at the beginning. I really want to see a lot of discoveries like gene therapies that come out from the UAE for our kids back in the country,” he said.
Five Emirati doctors are also taking part in a fellowship at the hospital. Paediatric surgeon Alia Al Belushi said being at Great Ormond Street has helped her improve her surgical skills and knowledge.
"You're learning from the best. In terms of surgery, it's not about being able to perform a procedure, it's about being able to perform it with excellence,” she said. She hopes to use her experience to establish a new paediatric urology unit in the UAE.
Prof Maha Barakat, assistant minister for medical affairs and life sciences at the UAE Ministry of Foreign Affairs, said the centre had, in a short time, "demonstrated the effectiveness of a pioneering model that combines world-leading research expertise with advanced clinical care, all within state-of-the-art facilities, transforming young lives".
Innovation
The centre is also exploring new uses of AI technologies to assist doctors in their work and streamline the hospital’s operations. It is piloting an ambient AI system, which would take clinic notes on behalf of doctors, and can generate a clinic letter within one to three minutes after the appointment has ended.
“The whole purpose of the capability is to see if AI can be used to improve a patient's experience and also improve a clinician experience of delivering care,” said head of innovation Stephen Mathew. But there are many hurdles to overcome before it can be rolled out, such as ensuring the AI doesn’t “make up” an answer, and that there are ways to monitor the AI’s accuracy.
“We often hear about AI solutions hallucinating sometimes. If it doesn't know the answer, it will make up an answer. That can have a significant impact on a patient's care [and] a detrimental impact on a child's life,” he explained. “So it's making sure guardrails such as those are around.”
In the long term, Mr Mathew hopes to see AI being used to provide personalised treatment for patients, by drawing on the data captured from all past patients.
“Can we use that data to understand how does this patient's current pathway compare to other patients we've seen in the past? How were their outcomes? What were the tests and investigations that would have aided that particular pathway? And how can we apply that?” he said.
