Toddler doing well after receiving newest gene therapy available on NHS

Now at almost three-years-old, Gunreet has the rare condition aromatic l-amino acid decarboxylase (AADC) deficiency and has been treated at GOSH for most of her life.

Thanks to a life-changing gene therapy commissioned by NHS England, she has gained skills previously out of reach for her, like vocalising and movement. As she grows up, the specialist hospital teams that care for her are hopeful she will make further strides to a life like peers.

AADC deficiency is an inherited disorder that is caused by mutations in the gene that produces the AADC enzyme in the body. It affects the production of chemical messengers called neurotransmitters. Without enough AADC, the body doesn’t have enough neurotransmitters (like serotonin and dopamine) to send signals through the body. This means that it becomes hard to control the head, neck, face, blood pressure and heart rate.

The condition is rare but often fatal, affecting every aspect of young life – physical, mental and behavioural development. Children with AADC deficiency have painful episodes where their bodies contort and stiffen, and their eyes roll out of their control, digestive issues, low blood sugar levels, behavioural problems, and poor sleep. Children with AADC deficiency often do not reach adulthood as they are prone to dangerous respiratory infections and can even stop breathing during their episodes.

GOSH treats nearly all the children diagnosed with AADC deficiency in the UK and is the only site for the potentially lifesaving and life-changing gene replacement therapy, eladocagene exuparvovec.

It is a one-time gene replacement therapy that contains the functioning DDC gene. It’s delivered directly into the brain via an infusion with millimetre accuracy in robotic-guided surgery, guided by a multidisciplinary surgical team using state-of-the art positioning systems.

When a functioning DDC gene is delivered to the exact part of the brain involved in the control of body movements (the putamen), AADC can be produced, leading to the production of much needed serotonin and dopamine which improves the symptoms of the condition.

It is the first NHS England commissioned brain-delivered gene therapy in the UK and represents a growing list of gene therapies available on the NHS in England, including treatments for sickle cell disease, beta-thalassaemia, spinal muscular atrophy and other rare conditions.

Gunreet was just nine months old when she was diagnosed with AADC deficiency. Mum Sandeep, from Hayes in west London, said: “When Gunreet was about seven months old, I noticed she wasn’t reaching her milestones at the same age that her older brother did. She couldn’t hold her own head up or reach out for items. She cried a lot and always wanted to be held.”

After Sandeep spoke to their health visitor, she took Gunreet to their local hospital where they did some tests.

Mum Sandeep continued: “Gunreet had some tests in hospital and then back with our GP, but it still wasn’t clear what was wrong with her. Then a few weeks later she caught a nasty respiratory virus known as RSV and was admitted to hospital where she had an oculogyric crisis, when her eyes moved upwards without control and so we were transferred to GOSH.”

After Gunreet arrived at GOSH she underwent genetic testing and was diagnosed with AADC deficiency.

In February 2024, she underwent the specialist surgery to have the new gene therapy. To date, Gunreet is the youngest patient to be treated under the NHS with this gene therapy and has made great progress.

Sandeep continued: “Since having the gene therapy, Gunreet has made great progress. She cries less, smiles more, and can reach for objects. She can hold her head up and is trying to sit up, she’s recently learnt how to roll from her stomach to her back which is fantastic to see.

“It means a lot to me that Gunreet was able to have this gene therapy. Her sweating has completely stopped, as previously she would sweat a lot and wasn’t able to wear a coat in winter as she would be too warm. She has a lot more control over her neck and her general health has improved. She has more coordination, she can bring her palms together and is able to move her hand to her mouth.”

Gunreet’s learning development will be monitored and the family hopes she will be able to start a school with specialist support for her in January next year thanks to the progress she has been making.

Professor Manju Kurian, consultant paediatric neurologist at GOSH and co-theme lead at the National Institute for Health and Care Research GOSH Biomedical Research Centre, said “AADC deficiency is a rare condition but often a cruel one that has such a profound impact on children and their carers and families. We know children with the condition have painful episodes that can last for hours and, as their condition progresses, their life becomes more and more difficult. It’s incredible to me that I can now prescribe novel gene therapies just as I would prescribe paracetamol and antibiotics.

“While the treatment is now available under the NHS at GOSH, we can only do this by working collaboratively across teams inside and outside the hospital, from physios and surgeons to dietitians and speech therapists, alongside partnerships with companies who supply these therapies.

“It’s great to see how this treatment has been able to help babies and children across the country like Gunreet. The natural history of the condition is that most patients cannot fully hold their head or make any developmental progress after that milestone. Gunreet’s progress over the last year has been really impressive in that context, as well as the virtual disappearance of the eye crises. We’re hopeful that one day she will be able to talk or walk, as seen in some of the young patients treated in the clinical trial.”

For the first time in the UK, specialists from the Department of Nuclear Medicine at University College London Hospitals and the Department of Developmental Neurosciences at University College London Great Ormond Street Institute of Child Health have visualised the effects of the cutting-edge gene therapy on the brain using advanced pioneering F-DOPA PET scanning. This provides concrete evidence of changes in the neurotransmitter activity in the brain, pre and post treatment.

Professor James Palmer, NHS medical director for specialised commissioning, said: “This is wonderful news for Gunreet and her family, and a powerful example of how these commitments are translating into real improvements in people’s lives.

“Over the last decade, NHS England has commissioned a pipeline of innovative gene therapies across a range of rare conditions, including treatments with the potential to cure patients.

“By bringing cutting-edge medicines like eladocagene exuparvovec into the health service and setting up our expert clinical teams to successfully deliver them, the NHS is making clear its commitment to improving care through innovation.”

Gunreet visits various teams at GOSH every three to six months and will receive life-long follow up care.