Pioneer Winter 2017

WINTER 2017 Great Ormond Street Hospital Children’s Charity

NEVER LOSING HEART

Elliott’s family waited over a year to find the donor that would save his life

LISTENING OUT FOR A SOLUTION An electronic device restored Paris’ ability to hear

PREDICTING AUTISM Pioneering study could help to predict autism in babies with a rare genetic disease

CONTENTS 04 AROUND THE HOSPITAL The latest news from Great Ormond Street

Hospital (GOSH).

06 ELLIOTT’S TRANSPLANT JOURNEY Elliott waited over a year to find the right donor for

his heart transplant. Meet the multi-skilled team who supported him and his family.

09 EXAMINING ENCEPHALITIS:

A BRAINY SOLUTION Dr Julianne Brown and GOSH patient Katie share

their venture to discover the cause of encephalitis – a life-threatening swelling of the brain.

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13 I HAVE… A COCHLEAR IMPLANT Twelve-year-old Paris talks to Pioneer about how her hearing deteriorated overnight and how an electronic device has restored her ability to hear.

16 PREDICTING AUTISM Pioneer finds out how a behavioural study aims to predict which babies with a rare genetic condition will develop autism.

20 THE PIONEER INTERVIEW Professor of Pathology Neil Sebire discusses the

potential of harnessing the hospital’s archive and how a new digital system could revolutionise every aspect of the hospital’s work.

23 CUTTING OUT GENETIC DISEASE Pioneer explores the way gene editing – altering a patient’s DNA – could rewrite the futures of seriously ill children.

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27 WHY I SUPPORT THE CHARITY:

JAMES HATCHLEY Non-Executive Director James Hatchley tells Pioneer how his very personal experience at GOSH fuelled his drive to complete multiple sporting fundraising challenges.

28 FUNDING LIFE-CHANGING CHILD

HEALTH RESEARCH ACROSS THE UK Find out about the exciting research projects that

Great Ormond Street Hospital Children’s Charity and Sparks charity are supporting across the UK.

30 A PARENT’S PERSPECTIVE Sam shares her story of finding out that both of

her daughters were born with a rare, non-genetic condition that caused both of them to be temporarily paralysed.

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WELCOME Every day, staff and researchers at Great Ormond Street Hospital are striving to change lives, whether they’re treating children on the wards, working in operating theatres or studying in the laboratories.

In this issue, Dr Julianne Brown and patient Katie share their race to discover the causes of encephalitis, a life-threatening swelling of the brain. Katie provides a personal account of her experience of the condition, while Dr Brown offers insight into the incredible advances that are helping to improve diagnosis.

Hearing about young people’s experiences battling the toughest and rarest conditions reinforces our unending drive to help the seriously ill children who need us the most. It’s always great to hear from their parents too, like Sam, whose daughters Amy and Mia were both born with a rare inflammatory disorder of the nervous system that causes paralysis. Mum Candace also tells Pioneer about her experience at GOSH with her son Elliott, who spent over a year on a Berlin Heart machine to keep his heart beating.

Candace and Sam’s experiences help to remind us of the life-changing impact GOSH’s work and support has not just on the children, but also on the families visiting the hospital.

Researchers funded by Great Ormond Street Hospital Children’s Charity (GOSH Charity) are not only working to cure and treat the vast range of complex childhood conditions, they’re trying to predict them and prevent them from developing altogether.

One group putting this into practice is Professor Mark Johnson’s research team at Birkbeck University, who are supported through the charity’s national research fund. They are looking for early indicators to predict which children with the genetic condition neurofibromatosis type 1 are most likely to develop autism. The team gave Pioneer a guided tour of their laboratories and the advanced scientific equipment they use, before explaining how predicting a diagnosis could help families get the support they need sooner, or even prevent the condition from developing altogether.

We’re all so incredibly grateful of your support of GOSH. I hope this issue of Pioneer demonstrates the amazing difference the hospital makes because of your incredible support and the collaboration of everyone at the hospital and charity. Together we’re helping to give seriously ill children a better future.

“ We’re all so incredibly grateful of your support of GOSH. I hope this issue of Pioneer demonstrates the amazing difference the hospital makes because of your incredible support and the collaboration of everyone at the hospital and charity.”

Thank you.

Tim Johnson Chief Executive Great Ormond Street Hospital Children’s Charity PIONEER 3

AROUND THE HOSPITAL BREAKTHROUGHS IN BRAIN CANCER RESEARCH COULD LEAD TO BETTER TREATMENTS Great Ormond Street Hospital Children’s Charity is one of four charities to fund a study by Newcastle and Northumbria universities, resulting in a promising new discovery about children with medulloblastoma.

Medulloblastoma is a type of cancerous brain tumour that requires treatments including surgery and radiotherapy. The study has identified that medulloblastoma can be categorised into sub-groups that each react differently to treatment. This finding can then be used to offer more personalised, effective treatments for children with the condition.

Evie (pictured 11 years old) was just one year old when she went into anaphlyaxis

SPARKS RESEARCH WILL BENEFIT ALLERGY PATIENTS Denisa has medulloblastoma and supported GOSH at RBC Race for the Kids in 2016

Scottish schoolboy first to be treated at GOSH and go home with HeartWare device Ten-year-old James Robertson is the first child fitted with a HeartWare cardiac device at GOSH to be allowed home to Scotland. James has myocarditis – an inflammation of the heart muscle – and needed surgery to fit the device which is now keeping his heart pumping while he is waiting for a transplant. He is one of just 12 children who have been fitted with the device at GOSH and in September, James left intensive care for the first time since July. Once his parents felt comfortable with operating the device, James was allowed home.

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Earlier this year, Sparks Children’s Medical Research Charity became a part of GOSH Charity and began working towards increased funding for pioneering and life-changing research, to benefit even more children, such as eleven year old Evie.

Evie is taking part in a study to investigate the genetic factors involved in the development of allergies. When she was just a year old, Evie had an anaphylactic shock in reaction to some peanut butter her family was eating nearby. She was rushed to hospital and later discovered she not only had a severe peanut allergy, but also allergies to eggs, sesame and dairy.

Professor Somnath Mukhopadhyay is leading the research project Evie is taking part in. Thanks in part to funding from Sparks, he is studying families to determine if genetic factors and a child’s environment may increase the chance of them developing an allergy. The aim is to develop a simple test that identifies whether children have a skin barrier defect which allows substances to pass through the skin and trigger allergies. This could help clinicians by giving them the opportunity to enhance children’s skin barriers and potentially stop children from developing an allergy altogether.

AROUND THE HOSPITAL New technology saves diabetic patient with insulin allergy A patient at Great Ormond Street Hospital has just become the first child in the UK, and the fifth in the world, to be fitted with a secondgeneration DiaPort system. Nine-year-old Taylor was first diagnosed with diabetes aged two but has a severe skin allergy to insulin. The DiaPort system is adapted to deliver insulin directly into the abdomen, bypassing the skin completely. Taylor was successfully fitted with the device last month. “I hope the DiaPort system will help Taylor to have a chance at being a normal little boy, back in school and playing with his friends,” says Taylor’s dad, Scott.

COMPLETION OF THE MITTAL CHILDREN’S MEDICAL CENTRE In November this year, the Premier Inn Clinical Building opens its doors to the staff, children, young people and families at GOSH. This key milestone marks the completion of the Mittal Children’s Medical Centre, following the opening of the first part of the centre, the Morgan Stanley Clinical Building, in 2012.

The new building will help the hospital to treat thousands more children thanks to new inpatient wards, more operating theatres and a day unit for children recovering from procedures involving anaesthetic. It will contain a new surgery centre, respiratory unit and a specialist ward for children with severe forms of arthritis, skin conditions or infectious diseases.

An official opening event in early 2018 will be an exciting opportunity to celebrate this important achievement with hospital staff, patient families and the charity’s important supporters, without whom this new centre wouldn’t have been possible.

A new theatre in the Dorfman Surgery Centre will allow the hospital to treat even more children The new building is designed around children and young people

GOSH ARTS RECENT COLLABORATION Artist Davina Drummond worked with young people at GOSH to create a limited edition set of temporary tattoos that explore and share what it means to be a young person in hospital. The project was led in collaboration with GOSH Arts and allowed young people to reflect on how they cope with their illnesses and process their hospital experiences. Davina and illustrator Ella Bell then transformed the young people’s concepts into a set of temporary tattoos, which are available to all young people at the hospital.

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ELLIOTT’S TRANSPLANT JOURNEY Elliott was diagnosed with dilated cardiomyopathy, a disease of the heart muscle, when he was just 12 days old.

He was kept alive on a mechanical heart – a Berlin Heart – for more than a year at Great Ormond Street Hospital before being given a heart transplant that has transformed his life. Pioneer talks to Elliott’s mum and the hospital team who helped him on his transplant journey

CANDACE Elliott’s mum “GOSH staff tried to make life as normal as possible while we were waiting in hospital. They made things fun for him and planned trips out, even if it was just around the corner to Starbucks. That was a major thing for us! Just getting him out of his room was a big ordeal.

“After a year waiting, I saw a missed call from GOSH and I thought, if they’re ringing this early in the morning it’s either really good or really bad. I rang back and the transplant nurse said: ‘I’m sure you know why I’m calling,’ and I said: ‘You’re going to have to say it!’

“You feel so happy, but you’re also frightened because you know he’s going into a major operation. You also can’t help thinking there is a family who’s just lost their child and that’s why this is possible – they decided to make something good come out of that. You feel every emotion simultaneously.

“The day we left, the transplant doctors walked out to the car with us and as we were saying goodbye, I started crying. They asked why and I said: ‘Because there were times I didn’t think that this day was ever going to come.

You’ve given me my son back.’”

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“ The day we left, the transplant doctors walked out to the car with us and as we were saying goodbye, I started crying. They asked why and I said: ‘Because there were times I didn’t think that this day was ever going to come. You’ve given me my son back.’”

Elliott’s mum Candace

EMMA SHKURKA Physiotherapist “When Elliott first came to the Cardiac Intensive Care Unit (CICU) he was acutely unwell – that’s when I first met him. His heart was failing and he was very weak. He could barely stand. I looked after his lungs while he was ventilated by a breathing machine. I helped him cough and made sure he didn’t get a chest infection. I also worked on his rehabilitation – helping to build up his muscles and reach developmental milestones like crawling and walking.

“With somebody Elliott’s age we’re not going to do lots of specific strengthening exercises, and its more about trying to make it fun. So we did obstacle courses where he had to climb, crawl and walk up and down stairs. We even got him peddling a little bike.

“After the Berlin Heart operation, Elliott’s recovery process was very slow because he was so weak. But once he was on Bear Ward we were able to take him to the roof gardens and gym, and he started to flourish. The posttransplant recovery was much shorter and he was able to get back on his feet much quicker because he’d been in such good physical condition before the transplant.”

DR JACOB SIMMONDS Consultant Cardiologist and Transplant Physician “I was part of the team monitoring all of Elliott’s non-surgical needs.

“When he felt well enough, I would take him to the playground behind the hospital on the Berlin Heart – which is not easy to do. The Berlin Heart moves like a huge shopping trolley, but it weighs twice as much.

“When the transplant came it was a massive relief. The day he left hospital was great for everybody. It’s always great to see someone go home after transplant when they’re well. Since then he’s gone from strength to strength.

“Now we see him in clinic every two months. His development is delayed because of the environment he grew up in – he was in a single room for most of his early life and he had lots of people doing things for him – but his speech is really coming on. Every time we see him it’s a boost to see how he’s developing into a little boy.”

Emma Shkurka and Dr Jacob Simmonds on Flamingo Ward

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Maura O’Callaghan trained Elliott’s mum in how to change his dressings

MAURA O’CALLAGHAN

SARAH MEAD-REGAN

WENDY STOKES

Lead Nurse for ECMO (Extra Corporeal Membrane Oxygenation) and VADS

Clinical Nurse Specialist and Recipient Transplant Coordinator

Play worker

“I’m the Lead Nurse for the Berlin Heart device. My role was supporting the family and completing clinical assessments of Elliott and the Berlin Heart device. There are three clinical nurse specialists in my team and we saw Elliott at least once a day.

“As Elliott’s transplant coordinator, I liaised with all the teams involved in Elliott’s transplant process. The transplant process involves 50 to 60 people including perfusionists (who assume the function of the heart or lungs in medical procedures), surgeons, theatre nurses and the CICU team. I was called at 1am with his transplant offer and he went to theatre at midday – that’s 12 hours of negotiating.

“Elliott was on the Berlin Heart for just over a year – first in intensive care, then on Bear Ward. Part of my role was to train his mum and dad in changing his dressings. We also did Berlin Heart competency training with them so they could have some family time without a medical person being in the same room.

“A clinical nurse specialist did a physical assessment of Elliott every day. The cannulas (plastic tubes) that went into his heart came out through the skin and, like any wound, they sometimes became sore and needed dressing. The Tissue Viability team advised us on how best to treat the wound and the play specialist came in to keep Elliott occupied.

“Elliott built up relationships with all the nurses. He didn’t speak a lot back then, but he used a sign language that we understood. He was playful, smiley, cheeky and had real character. His mum and dad were amazing – so resilient. We looked forward to seeing them and catching up with them. In a way, we became like extended family.”

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“I remember the phone call to the family telling them there was a donor.

It was only a provisional offer at that stage, but it was a special call to make. It took such a long time to find a match because of the lack of paediatric donors, the size of the donor and needing to find a donor of a suitable blood group. This was Elliott’s first offer.

“As the months pass and there is still no donor, it becomes hard for the family to stay strong. It was particularly tough for his mum who didn’t leave the hospital the whole time Elliott was here.

“As transplant coordinator you end up having a close relationship with the family because you’re waiting with them and supporting them through that long, difficult time. The actual transplant is an emotional event for both the team and, of course, for the family.”

“Elliott always let you know what he liked and didn’t like. You wouldn’t get away with taking a basic car or dinosaur in for him. It had to be something more interesting – like a car with a dinosaur inside of it!

“I first met him when he came to Bear Ward, and then I saw him every day. I’m based on the ward to keep the children’s development up to spec and to provide daily play projects, so I would try to provide him with the equipment he’d get in nursery or pre-school.

“He loved messy play, so we had a big tray with penguins and polar bears in it and we’d use a flour dredger to make it snow. That was his favourite and it would end up all over him.

“One of my most important roles was to be with him when he had his dressing changed. A nurse trained his mum to do it. At first he used to cry because it was very painful, but he got so used to it.

“I used to stand at the foot of the bed and hold his hand, and we would sing and talk. It was only once he was in this position that his mum would start. He knew what the whole dressing procedure entailed and he could almost talk her through it. It was amazing – he is amazing.”

Katie’s encephalitis was caused by a problem with her immune system

EXAMINING ENCEPHALITIS: A BRAINY SOLUTION Encephalitis needs to be corrected quickly, but as Katie found out, when you’re against the clock, finding the right treatment is tricky

Katie was shopping with her sister when she had a seizure that lasted two hours. As Katie was rushed to a local hospital, she was unaware that her seizure was a symptom of encephalitis – a swelling of the brain. She was a healthy teenager, so how had she developed encephalitis? The race to discover what was causing the swelling had begun

A RISKY DIAGNOSIS While uncommon, encephalitis can be life-threatening, and prompt treatment is essential in order to reduce the swelling and risk of permanent brain damage. But diagnosis is complicated because a patient’s encephalitis could be caused by an almost overwhelming number of factors. Viral, bacterial or fungal infections can cause encephalitis, as can autoimmune conditions – in which the patient’s immune system attacks their own brain.

To make the stakes higher, patients require drastically different treatment depending on the cause. If a patient’s encephalitis is caused by an autoimmune condition, medical staff may prescribe drugs to dampen the patient’s immune system. In a patient with encephalitis caused by a virus or bacteria, the immune response is essential for fighting the infection – if the patient’s immune system is dampened this allows the infection to get worse.

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WARNING SIGNS Shortly before her seizure in the shops, Katie also had what is called an ‘absent seizure’ at school.

“The way I described it was like someone walking across my grave,” explains Katie.

“That’s what it felt like. You can see everything happening but you’re not really there.

“One of the things that makes my illness so tricky is that I’m not aware that I’m getting ill. I was probably ill six to nine months before my first big seizure. Some of the signs are being aggressive and having panic attacks, my handwriting gets messy, I find it difficult to concentrate and my audio processing goes out the window.”

Katie went on to suffer more seizures at her local hospital, staying in the intensive care unit three times over three weeks. Her medical team decided that she needed specialist care and she was transferred to the intensive care unit at Great Ormond Street Hospital.

“ In many ways, it’s a blessing that I can’t remember most of what happened to me,” says Katie. “I spent two days in intensive care at GOSH and the only thing I remember are vivid dreams, which were based on the things around me. I was there but I wasn’t there.

They call it a delirium.”

SCIENTIFIC SUPPORT Joining Katie on the discovery to find the cause of patients’ encephalitis is Dr Julianne Brown, a clinical scientist in the Microbiology, Virology and Infection Prevention and Control team at GOSH. “Part of my job is adapting existing techniques for clinical use,” explains Dr Brown from her office in the Camelia Botnar Laboratories. “I take techniques which work really well in research, but might take a month to get results, try to streamline the process and make it available to patients in the NHS.”

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One such process is the use of a genetic screening technique called ‘high throughput sequencing’, also known as ‘deep sequencing’.

This technique promises to greatly ease diagnosis for encephalitis, ultimately speeding up the time it takes to diagnose and treat seriously ill children.

“ A brain biopsy and cerebral spinal fluid are really precious samples as you can’t just keep taking them from patients.

So you have to prioritise what you look for.”

Dr Julianne Brown

Dr Julianne Brown uses a technique to help speed up the diagnosis for encephalitis

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Searching for the cause Dr Brown explains that the hunt for a cause often starts with a “good guess”. Rather than feeding a patient’s sample into a machine and getting an answer out at the other side, clinicians must anticipate what might be causing their patient’s encephalitis and then test based on their guesswork.

The most common cause of encephalitis is herpes simplex virus (HSV) – the virus which causes cold sores. If this is the suspected cause of a patient’s illness, clinicians will prepare a fluorescent, chemical probe set to ‘switch on’ if it comes into contact with HSV. If the sample fluoresces, then the clinicians know what is causing their patient’s encephalitis. If it doesn’t, then they must try again with another likely suspect.

Katie remembers how stressful going through tests can be. “My condition is really rare,” she says. “And I was told that my diagnosis was a process of elimination. I know they did hundreds of tests, including CT and MRI scans, lumbar puncture, EEG and blood tests.”

*Glaser CA, Honarmand S, Anderson LJ, et al.

Beyond viruses: clinical profiles and etiologies associated with encephalitis.

Clin Infect Dis 2006; 43:1565–77

“There’s hundreds – thousands – of viruses and you can’t test for them all,” explains Dr Brown.

“There might not be enough sample. If you’ve got a brain biopsy or cerebral spinal fluid, they’re really precious samples as you can’t just keep taking them from patients. So you have to prioritise what you look for.”

As a result, between three and six in every 10 cases of encephalitis go undiagnosed*. Dr Brown hopes to change that by developing the ‘deep sequencing’ technique for clinical use, supported by Great Ormond Street Hospital Children’s Charity funding.

Deep sequencing looks at all of the DNA in a sample and matches it up to all known viruses and bacteria. She hopes the technique will offer clinicians and their patients an answer first time round, avoiding multiple tests and waiting times. How the sequencing technique works is complex, involving high-tech machines and super computers that ‘piece together’ the genetic jigsaw puzzle found in patient samples.

Making sense of the DNA Once a patient sample is obtained, the DNA within it is extracted and purified. This leaves a pot of human DNA sequences from the patient, and possibly also genomes from whatever is causing the infection.

Once the human DNA has been spotted, it is removed from the analysis. Scientists are then left with a heap of DNA sequences belonging to whatever is causing the patient’s encephalitis.

These fragments are pieced together and identified using a database of known causes of encephalitis.

Rather than using the ‘needle in a haystack’ approach, clinicians can get a match to any of the known causes of encephalitis, and this means medical teams can be more confident that the they’re prescribing the correct treatment.

A diagnosis for Katie A correct diagnosis has made a world of difference for Katie. “I have a type of encephalitis that is caused by something going wrong with my immune system,” she explains. ”Even though there was so much uncertainty around my condition and treatment, I knew I was in a special place at GOSH and that gave me a sense of security. I saw specialists from different departments come together to discuss what might work best for me. It gave me total faith in my doctors.”

The work that scientists, like Dr Brown, are carrying out is transforming the way the cause of encephalitis is identified and allowing young people like Katie to receive treatment faster and carry on with day-to-day life.

“I’ve had to learn to manage my expectations and prioritise my health, and that’s quite hard when you’re a teenager. I guess there’s a level of maturity in having to accept that I will always need to be very careful.

“I really needed to take something positive away from this. Otherwise I’d feel that it’s unfair and become very bitter and angry. GOSH has taught me to put one foot in front of the other and be grateful for everything you have. I’m brave, mature and responsible, and GOSH has given me that.”

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I HAVE… A COCHLEAR IMPLANT When 12-year-old Paris’ hearing started to deteriorate, she was referred to the Cochlear Implant team at Great Ormond Street Hospital, who recommended an electronic device that could help her hear again PIONEER 13

“Growing up deaf, there have been some hard times and some easy times.

I don’t always understand what people are saying, but if they’re deaf aware for example, they get my attention with a tap on the shoulder, take their time and look at me when they talk so I can read what they’re saying – it’s much easier “Being deaf affects everyday things, like listening to the train tannoy – I don’t always understand an announcement – or if we’re in a noisy place, it’s hard to make out what people are saying. At school, group discussions are hard, because I don’t really know what people are saying, especially if everyone is talking at once.

“I don’t let being deaf hold me back – I try to do everything!

It’s just that sometimes I’ll need an extra bit of help and it can take me a bit longer. For example, I went waterskiing at the Bluebird Deaf Water Ski Club and the friendly signing instructors helped me communicate by signing from the side of the boat. My brother, Josh, who doesn’t

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have any hearing problems, was really quick at standing up on the skis. I took a bit more time, but because I could sign, it meant I could still take part.

“I’ve had hearing aids since a baby as my condition was identified as part of the NHS newborn screening programme. The aids had always been enough to help me.

My family and friends have always been patient with me and used sign to explain what they’re saying. They know how to be deaf aware, and they support me. My mum and Josh are both able to use sign language, so they can help me if I need it.

“At the beginning of this year, my hearing got worse.

Some of the high-frequency sounds I was used to hearing disappeared overnight and I lost hearing in my left ear.

My doctor referred me to Great Ormond Street Hospital where I was assessed by the Cochlear Implant team.

“Me and my family did some research, and after my assessment, we found that a cochlear implant was a good option. It’s an electronic device that helps to carry the sound signals to my brain so that I have more access to sounds. When you first get the implant, sounds come out as beeps. Over time, I’ll work to change those beeps into recognisable sounds.

“I felt nervous and a little bit excited about coming to the hospital for the first time. I was nervous because it was all

“ I like the people who work at GOSH. The play specialists at the hospital really support me. If I’m feeling really anxious or stressed, they help to calm me down by talking to me and giving me things to do.”

Paris’ mum and her brother, Josh, both use sign language to support her

new for me and I was thinking about the cochlear implant.

But the hospital was also exciting, and I like going to London, especially to the parks and the Science Museum.

“I like the people who work at GOSH. They’ve always gone above and beyond to help me, particularly the hearing therapist Tina Hill, who has supported me throughout the whole process. She even visited me at school. I was anxious before my operation and she gave me strategies to cope with anxiety when I’m at hospital, which has really helped.

“I’ve just become involved in the 100,000 Genomes Project, which is looking at discovering the causes of some rare diseases. I recently came to the hospital with my uncle – who is also deaf – and Josh to see if there’s a genetic link.

“GOSH isn’t like a normal hospital. There are different places you can go to take your mind off things. I like all the lights in the hospital’s restaurant, The Lagoon – it’s like a rainbow. When I was going into surgery, there were lightup animals – like butterflies, bees and deer – on the wall that moved along with you.

“For other young people who are thinking of getting a cochlear implant, I’d say that it’s worth a try. But it’s your choice – you’re not pressured into getting one, and you should do some of your own research.

“I might get a second one. I can only hear beeps at the moment, but the changes will happen, over time.”

Paris enjoys exploring London’s parks and museums when she visits the hospital

HOW DOES A COCHLEAR IMPLANT WORK? A cochlear implant is a small, electronic device that helps to replace the function of a damaged inner ear, or cochlea. In most cases, hearing loss is caused by damaged hair cells in the cochlea, which are responsible for carrying sound signals to the brain.

Unlike hearing aids, which make sound louder, cochlear implants do the work of damaged parts of the inner ear to provide sound signals to the brain. While cochlear implants don’t ‘cure’ deafness, they can significantly improve a child’s ability to hear.

We perceive sounds at different frequencies.

A high-frequency sound could be a bird chirping, while an engine roaring would emit a low-frequency. Hair cells that perceive high frequencies are at the bottom of the cochlear, and so they are usually affected first. It’s these high-frequency sounds that Paris is working to recognise again with the help of her cochlear implant.

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PREDICTING AUTISM Pioneering behavioural study aims to help predict which babies with a genetic condition will develop autism

Electroencephalogram nets help researchers to measure babies’ responses to stimuli

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Dr Emily Jones is part of the research team observing children with genetic disorder neurofibromatosis type 1

Until now, research into genetic condition neurofibromatosis type 1 (NF1) has consisted mainly of exploring the physical effects it has on people’s lives. But a new study at Birkbeck University, funded

by Great Ormond Street Hospital Children’s Charity, is set to discover more about the impact the condition has on children’s behaviour and whether it increases their likelihood of developing autism

ABOUT NF1

THE AIMS

Approximately one in every 2,500 children is born with NF1* and it’s diagnosed in two ways. For some, it runs in the family and the genetic mutation is inherited from parents.

For others, the mutation appears unexpectedly.

Every year, GOSH Charity invites researchers across the UK to apply for funding for innovative research projects to improve child health.

One successful application came from a team at Birkbeck University comprised of Professor Mark Johnson, Dr Emily Jones, Dr Jannath Begum Ali and PhD student Anna Kolesnik, who are on a mission to find the link between NF1 and autism.

It can affect multiple parts of the body and physical symptoms range from benign tumours, to a curved spine, a large head and high blood pressure.

When children inherit the disease, it’s often diagnosed prenatally by testing blood from the umbilical cord, but when it’s sporadic, it’s typically picked up in infancy through multiple café au lait spots – very pale brown skin discolorations – which affect about 95% of people diagnosed.

“Recently people have realised that autism is very common in children with NF1, and we’re trying to understand why that is,” Dr Jones explains. “What’s happening in their infancy that might predict whether they will develop these autistic behaviours?”

*Source: Evans DG et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet Part A 2010; 152A: 327–332

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Dr Jones and Dr Begum Ali hope to identify which children are most likely to develop autistic behaviours

RED FLAGS

THE MONITORING

By conducting observations of babies at five, 10 and 14 months old, they’re hoping to find biomarkers – measurable characteristics – that can help them to identify which babies have an increased risk of developing autism. Spotting these early warning signs could give clinicians and parents the chance to either slow the progression of autism, or prevent certain behaviours from developing altogether. Most of all, identifying these signs will ensure children with autism are given the right support from a young age.

So far, there are 12 families involved in the study. Assessment begins before they even set foot in the laboratory, as parents are asked to fill in a questionnaire about their infant’s general development leading up to the visit. Dr Begum Ali says: “It’s things like measuring milestones. Is the baby sitting up yet? Are they crawling?

Questions about temperament and sleep diaries. We add a few language development questions when they get to 10 and 14 months old.”

Once the family arrive, they’re taken downstairs to a cluster of small laboratories. Then the observations begin. Children sit on their parent’s lap in a curtained room with low lighting and are shown stimuli on a screen. “We track where they’re looking and how long they’re looking for,” Dr Begum Ali explains. “We also record their heart rate – if it increases or decreases – to measure their levels of engagement.”

Next, the team conduct a series of behavioural play games. Dr Begum Ali says: “We have a puppet show and we

“At the moment, we don’t know how to spot the biomarkers,” Dr Jones says. “We have to wait until the children are about three years old. Then we’ve got to look back on the data, so it’s a really slow research process.”

Puppets are used to engage with the babies

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Five-month-old Nathan is taking part in the study

see how they react when the puppets disappear. We have frustration tasks where we give them something and then take it away to see how they respond. They do get a bit frustrated.”

Dr Begum Ali and PhD student Anna even sing to the children as part of a live action element of the study. “We look at natural brain responses to people mimicking things that infants have previously seen on screen,” says Dr Begum Ali.

CAPTURING RESPONSES Brain response and activity is captured using an electroencephalogram (EEG) and near-infra red spectroscopy (NIRS). Both techniques are risk-free, non-invasive ways of recording how babies’ brains interpret information from their surroundings, by using sensors attached to their heads.

“NIRS is a bit like an MRI. It is a very weak light that we shine into the brain. Because babies have such thin skulls, the light goes through them and bounces off the brain, then reflects differently based on the colour of the blood,” Dr Jones explains.

These differing reflections are dependent on the amount of oxygen in the blood. When blood has a lot of oxygen in it, it looks red. When blood has less oxygen, it looks blue. Dr Jones says: “NIRS measures the amount of red and blue light bouncing off the blood flow in the brain.”

Highlighting the amount of oxygen present in certain areas of the brain helps the team to distinguish how a baby is processing information. Dr Jones says: “When parts of the brain become active, initially they use up loads of oxygen, so the blood gets bluer. Then you get an over-supply of blood that brings lots more oxygen to the brain region to help keep it working, so you get an increase in red blood.” The team use this information to determine which areas of babies’ brains are active in different situations and when responding to different stimuli.

“What we’ve found before is that when you show videos of people to babies with a high risk of developing autism, they don’t show the same activation over the right brain regions that typically developing babies

do. Typical babies will activate the temporal lobe above the ear, which is a social brain region. Infants with a higher chance of developing autism don’t,” says Dr Jones.

COMPARING DATA To interpret results, the team need to compare them with control groups.

“We see babies without NF1 who are at risk of autism and ADHD (because they’ve got family members with autism and ADHD), low-risk typically developing babies and a control group with no autism or ADHD in firstdegree relatives,” says Dr Jones. “We take our EEG and NIRS data and, by the time they get to age two or three, group the children on whether they meet the criteria for autism or not, and look back at their infant data.”

This study has been running for two years, so the team are already collecting reams of data to analyse.

Dr Jones says: “We’re starting to get emerging signatures. The group of babies who go on to have autism are less likely to recognise and follow another person’s eye gaze, but at the moment findings are only significant at a group level. We’re trying to put data together to get better individual predictions.”

WORKING WITH FAMILIES

study are already benefitting from the process. Dr Jones says:

“A lot of families say they really enjoy it; they enjoy spending time with their baby and learning more about them.”

While the study is in full swing, the team also hope that monitoring behaviours will also highlight behavioural differences within the groups being observed. “Nobody has really studied babies with NF1 before and they may have behavioural delays quite early on,” Dr Jones says. “That’s important for doctors to know about as they might need to pay more attention to their motor skills or language skills.

There’s existing support strategies to try before autistic symptoms become established, so I think that’s potentially beneficial for families in the shorter term too.”

For now, the team remain dedicated to observing children in the laboratories, singing and measuring their responses in the hope that one day, they can help improve paediatric care by predicting the future.

It’s a while before results will show what the early indicators of autism are, but families taking part in the PIONEER 19

THE PIONEER INTERVIEW:

NEIL SEBIRE

“Medicine may move faster in the next 10 years than it has in the previous 100.”

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Embracing new ideas and innovations has always been a fundamental part of the groundbreaking work taking place at Great Ormond Street Hospital. Professor Neil Sebire is at the heart of two of the hospital’s projects working with very old data and brand-new technology As a Professor of Pathology, Neil Sebire has recently led research into harnessing the power of the hospital’s extensive archives to improve the identification of childhood cancers. His findings hit the national press and could lead to many more important discoveries that could improve care for such conditions.

His role as the hospital’s Chief Research Information Officer has also seen him play a big part in developing the hospital’s brand-new electronic patient record system (EPR). The EPR is more than just a software programme. It has the potential to transform every aspect of hospital life and improve the experience of patients, families and staff. The charity has a critical role in funding this project.

Pioneer spoke to Neil about the importance of his research and the arrival of the EPR.

Why did you decide to investigate the hospital’s archives?

One of the biggest problems with paediatric tumours and anything that is tissue-based is that, in general, given the effectiveness of modern treatments such as radiotherapy and chemotherapy, there’s hardly any viable tumour left when they are removed. That’s very good for the patient, but it means that there’s very little tissue available for genetic studies.

However, material from tumours is routinely taken for diagnosis and stored in paraffin wax as part of the hospital’s records. Our archive

contains thousands of specimens stretching back to the 19th century, but until recently, it had not been possible to use them for genetic testing.

Out of curiosity, we tested samples taken from around the 1920s, which is when we’ve got fairly good handwritten documentation about each specimen. We looked at those under the microscope, identified them, and then tried to extract the DNA from them. We tested them as we would with any other sample, and found that the quality of the DNA was exactly the same as if we’d taken it a couple of weeks ago.

If we could harness more archives, we could do a lot of work that we can’t do now.

What makes the GOSH archive unique?

It’s relatively unique in terms of how far back it goes. Every hospital that has a pathology department has a diagnostic archive because they are kept as part of the patient record.

But many departments will have got rid of their older specimens over the years. Given that GOSH has had a pathology department from when the hospital first opened in 1852, we have got many specimens to investigate and fairly good written records going back for nearly a century. That is unusual. And obviously, given the very rare conditions that GOSH has been involved with treating during that time, the samples themselves are often particularly unusual, if not unique.

cancer, for example, that’s very common, so if you wanted to collect 100 cases it’s not that hard. But with a certain form of paediatric tumour, there may only be two or three cases a year. If you want 100 tumours to study, it’s going to take you decades to finish, whereas if you can unlock the diagnostic archive, you could potentially find the samples you need.

It would really mean a great deal for genetic studies into very rare diseases. Currently, it’s only tumours, but it could be any disease in theory.

With access to the archive, a study can use these amazing old samples to drive progress faster and therefore make a difference for patients sooner.

How would the archive information be stored, is this where the EPR comes in?

Good quality data will be stored and made available through the research platform that’s part of the EPR.

Could you tell us a bit about the EPR and how it’s going to work?

It’s hard for us to fully get our heads around, but this is much more than just a piece of software – it will become the backbone of the hospital and the cornerstone of every interaction related to GOSH. The EPR is designed to amass and organise data and there are two aspects to the new system. Firstly, there’s the part that will collate information about patients, from the several hundred different digital systems across the hospital, into one accessible, centralised space.

The second part is a research and analytics platform, designed to work with the patient data and filter information for clinical trials and other research. This will give researchers access to information that could change patient care or inform new treatments, in a way that has never been possible before.

It has the power to speed up research and advance medicine.

Why is harnessing archive material in this way particularly significant for improving paediatric care?

In adult practice, it’s not so relevant.

If you’re doing something on breast PIONEER 21

Tumour samples, dating back nearly a century, are preserved in small blocks of paraffin wax

What difference will it make to the children at GOSH? The immediate impact will be to improve each patient and family’s experience in the hospital. It will give them access to groundbreaking research at home, make it easier for them to book appointments and make their hospital experience much smoother. For example, a patient may have tests done both at GOSH and another hospital. At present, the results are not available to all parties, so a test may be repeated if it’s not certain if it has been done. If you can reduce the number of times a duplicate test is done by having information more readily available, you speed up the time it takes for a test to come back by freeing up capacity in the laboratory. You avoid unnecessary needles too. Patients will also have immediate access to important information via the Patient Portal. They’ll be able to find out more about their condition and check when their next appointment or scan is.

In terms of the research platform, the main benefit to patients is that we can do research faster, more efficiently and with better governance. For example, this will mean if there was a clinical trial underway for children with cystic fibrosis between the ages of five and 10, at the moment it’s a very 22 PIONEER

manual system to find those patients.

However, the EPR can be set up with triggers, so that whenever a patient arrives at GOSH with those criteria, a notification will alert the relevant team that this new patient is eligible.

Once the patient has consented to that trial, you can then set up a dedicated space in the research platform for capturing all the information that’s required for that trial and organise it in a way that’s ready to analyse. It’s completely deidentified, so no researcher would know that that data is linked to that patient. This way, we can assure patients that their data is secure while pushing forward faster with those research projects, getting answers that could improve care and treatment more quickly. The system will also mine the latest research information to make recommendations to clinicians and, in the future, could support the use of robotics or virtual reality.

The EPR represents a big investment for Great Ormond Street Hospital Children’s Charity. Why is it important that the charity supports the hospital in these kinds of technical innovations?

In my opinion, the whole project will be the single biggest thing we will

do in the hospital for decades. I can’t wait to see what it achieves.

It could revolutionise the way we do research and the way we involve patients. Even if every project that uses the platform is only 5% or 10% quicker or more efficient, in the grand scheme of things, that’s a massive effect. It will also improve our ability to work with others, and to coordinate bigger clinical trials involving hospitals around the world.

The charity has supported research projects that I have been involved with in the past – with these, proving the value of such work is relatively straightforward. Someone says: “We paid for this project. What did you get at the end of it?” and you say: “We did this. We published this paper.

This is what we’re going to change.”

Those projects are very specific, so highlighting the benefits of the project’s outcome is relatively simple.

The difference with this project is that this is going to have an impact on potentially everything we do at GOSH. I believe it’s going to be one of the most important investments we’ll ever make, and GOSH Charity is at the heart of that investment.

The additional money the charity has given to this project means that we will have a system that positions GOSH ahead of the rest of the world.

CUTTING OUT GENETIC DISEASE Imagine if we could rewrite DNA, the body’s builtin instruction manual. We could cross out the bad instructions and create a manual for a healthy body instead of an ill one. Thanks to gene editing, research teams across Great Ormond Street Hospital and the UCL Great Ormond Street Institute of Child Health (ICH) are doing just that – starting a new chapter for medicine Each teams’ aims are similar – they’re modifying DNA to treat diseases – but there’s a range of projects out there, from creating cancer-killing cells to deleting faulty genes.

Supported by Great Ormond Street Hospital Children’s Charity funding, Dr Claire Booth has recently joined the ICH’s world-renowned Immunology team headed up by Professors Bobby Gaspar and Adrian Thrasher. She explains why genes are so important: “Our genes are a precise set of instructions that determine how our bodies look, grow and function. When errors creep into those instructions – by chance or because they’re passed on by our parents – they can cause disease. We can treat the symptoms of these conditions, but what we’re trying to do now is to fix the genetic mistake itself.”

One way of doing that is through gene editing. Dr Booth explains: “We take some cells from a patient, which carry the genetic mistake that’s causing their disease. Then we add in some ‘molecular scissors’ – proteins and molecules that are programmed to physically cut through the two strands of DNA – at a precise location. This means we could literally chop out faulty bits of DNA, or make it easier for new, corrective DNA to be delivered to the right place.”

There are currently three main tools used to edit genes– CRISPR, TALENS and zinc finger nucleases. Each has its benefits, but CRISPR is the newest gene-editing tool.

It acts like scissors to cut out faulty DNA and it has attracted a huge amount of publicity and funding.

It sounds like an exciting prospect, but there are hurdles to overcome before doctors can really start using gene editing to treat patients. Dr Booth says: “The main problem is making the process more efficient, so that enough cells are edited to make a difference when we give them back to the patient. The second is making sure we aren’t making DNA cuts in places we don’t want them, because that could cause new problems. We’re making really exciting progress in overcoming these difficulties.”

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TARGETING DNA DELIVERY Gene editing may still be in its infancy, but researchers at GOSH have been modifying genes in another way for a long time, using a technique called gene therapy. Dr Booth explains: “In gene therapy, we give patients a new healthy copy of the gene and it’s incorporated into their DNA at fairly random locations. Usually that’s fine, but ideally, we want to place that gene exactly where it would be in a healthy patient. Gene editing could help us do that.”

A more specific placement of that corrected DNA would benefit patients with complex immune system disorders like chronic granulomatous disease (CGD). In these conditions, the affected genes are only active at a certain time during the immune system’s development, or when an immune cell is performing a certain function. That makes placing the gene where it belongs even more important, says Dr Booth: “If we create a ‘cut’ at a precise point in the patient’s DNA, the corrected gene will insert itself there, exactly where we want it. That should make it function as it would in a healthy person, without any problems with when or how it ‘activates’.”

The team have successfully used gene therapy to treat patients with CGD, but now researchers Professor Thrasher and Dr Giorgia Santilli are looking into whether gene editing could make these kinds of treatments even better.

And they aren’t the only ones who see great promise in ‘molecular scissors’.

Find the faulty part of DNA that needs editing. Use molecular scissors to cut the DNA so the new edited gene knows where to go when it is inserted.

REMOVING PROBLEM DNA IN THE LABORATORY Under the supervision of muscle-wasting disease expert Professor Francesco Muntoni, ICH PhD student Veronica Pini is using gene editing to tackle Duchenne muscular dystrophy (DMD).

DMD is a devastating genetic disease that causes progressive muscle deterioration. Sadly, most children with the condition do not live past their late twenties or early thirties.* For around 10% of patients, their DMD is caused by a DNA duplication.** Instead of one gene telling the body how to make dystrophin – an essential muscle-building protein – they have two identical sections of DNA stuck together. When the body ‘reads’ this part of the instruction manual it doesn’t make sense, so no dystrophin is made and muscles are unable to repair themselves.

Using gene editing, Ms Pini is trying to correct this mutation by ‘chopping out’ the duplicated section of DNA, restoring the gene to its normal sequence.

In a landmark moment in late 2016, she used CRISPR to successfully restore dystrophin production in cells taken from a young person with DMD. Ms Pini says: “I really believe that CRISPR might one day be used as a therapy for DMD patients. Genome editing is the future.” *Source: ncbi.nlm.nih.gov/pmc/articles/PMC3476854/ **Source: ncbi.nlm.nih.gov/pmc/articles/PMC4931045/ (Date both sources visited: 26 September 2017)

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When DNA has two identical sections stuck together, the body can become confused. This duplicated DNA is chopped out so the gene can work properly.

GIVING CELLS SUPERPOWERS While there’s still a way to go for some applications of gene editing, Professor Waseem Qasim has already seen astounding results. In 2015, Professor Qasim used a pioneering gene editing technique to successfully treat two young children with a previously incurable type of leukaemia.

After taking some immune cells from the patients, Professor Qasim’s team used TALENS technology to edit the DNA. This careful editing gave each cell a new set of instructions, directing them to produce partly synthetic ‘cancer-killing’ receptors on their surface. Once returned to the patient’s bloodstream, these immune cells had a superhuman ability to track down and destroy cancer cells.

The children involved in this trial now have a unique, leukaemia-fighting ability built in to their immune system that is not naturally present in any other human being.

Professor Qasim says:

The DNA is edited to give cells new abilities that they wouldn’t naturally have.

HOW DOES GENE EDITING WORK? Gene editing tools act like molecular scissors, making precise cuts in DNA. They can be used to add, remove or alter carefully selected sections of DNA. This can help researchers understand diseases and develop groundbreaking new treatments.

“ It’s an exciting time for us. At the moment, we’re treating one type of leukaemia, but we think we can use this technique for other forms too.”

The team are developing a bank of ‘universal’ leukaemiakilling cells, sourced from healthy donors and edited to stop the patient’s body from rejecting them. These cells could be used to treat any patient, broadening the scope of this hugely promising therapy.

Gene editing could provide ill children worldwide with a new hope of not just treating the symptoms of their condition, but curing the root cause. With incredible strides in technology and our understanding of DNA growing each day, the future for genetic medicine looks bright.

“ Back in 2008 when I first heard about gene editing, the efficiency was so low that everybody thought it would be a huge challenge to get it to work in patients. Me included.

But in the past few years, there has been some extraordinary progress. I’m really excited to see what the future holds.”

Dr Claire Booth

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MEET LAKE One year ago, 17-year-old Lake took part in a gene therapy trial at Great Ormond Street Hospital to treat an immune system disorder that has affected him since birth. Now 18 years old, Lake is ready to start a new life in Cornwall

“Chronic granulomatous disease (CGD) is an immune deficiency, which means I get ill easier than other people,” says Lake. “Before I had gene therapy, I spent a lot of time at GOSH and was always taking time off school.”

“I used to have to take lots of medicine every day, but now I’m off almost all of it. I’m a lot more active, doing things like walking the dogs on the beach or going to the gym. I’m starting college this year too and learning to drive.”

When Lake hit his teenage years, his CGD took a turn for the worse. “The infections began to spiral out of control and Lake was very sick,” says Lake’s mum, Rachel. “That was when gene therapy was first mentioned. I’d known about it from an early age because my brother has CGD and I’m a carrier. Then I had Lake, and gene therapy started to become more prominent.

Over an 18-year period I’ve watched the science grow and develop.”

Rachel has noticed some big changes as well: “I see him carrying the hoover down a flight of stairs, when there was a time when he couldn’t walk down any stairs, let alone carry a Dyson hoover. It may seem silly, but it means the world to me. Before he had gene therapy, CGD really dragged Lake down. Now, he’s energetic, go-getting and full of spirit.”

Together, Lake and his mum made the decision to go ahead with the trial. “I was apprehensive because I’d heard stories about gene therapy not going that well in the past. But now they use different methods and there are lots of success stories,” says Lake. “The day I had the corrected cells given back to me, I was pretty ill, so I wasn’t happy or sad really. I just wanted to get it over with. But it turned out to be well worth it.

26 PIONEER

While he’s glad he went through gene therapy, it’s not something Lake takes lightly.

“ To someone else considering it, I would say it is worth doing but it’s not easy. I think it’s great that people like Claire Booth and Bobby Gaspar are trying to make gene therapy even better.”

JAMES HATCHLEY WHY I SUPPORT THE CHARITY

It is hard to describe how passionately I feel about the work the doctors and nurses do at Great Ormond Street Hospital When my 15-year-old daughter Emma’s health deteriorated unexpectedly early in 2014, everyone suspected some form of lung disorder.

Very sadly she had a dreadful and extremely rare disease called ChurgStrauss syndrome – an inflammatory disease that, unbeknown to us all, had badly damaged her heart and other organs. For four months the surgeons, doctors and nurses at GOSH did absolutely everything they could to save her, but tragically she lost her battle on 30 May 2014.

Emma spent all her time at GOSH in the cardiac intensive care unit. The building Emma’s ward was in, the nearby room my family stayed in, and many of the medical devices that kept her alive were all paid for by the charity. It’s a natural reaction to want to support both the people and the institution that help us in such selfless and practical ways.

In my case, I wanted to see if there was any way I could directly support the nurses and clinicians at GOSH. One idea was to offer my commercial and professional experience, together with all that I had learned Photo credit: Sportograf

as a parent of a child at GOSH, to the governance of the hospital. In September last year, I was fortunate enough to be selected as one of the hospital’s non-executive directors.

Another idea was to support Great Ormond Street Hospital Children’s Charity by fundraising. We created a fund called The Rosebud Appeal – Emma’s middle name was Rose – and this is one way we are ensuring her memory lives on. As a direct result, we have been able to fund a range of specific cardiac research projects, equipment and the employment of a PhD student to study the genetics associated with the disease Emma had.

Together with family and many friends, I have fundraised across a range of events. I compete in triathlons and encourage others, including staff from the intensive care unit, to join me. As well as enjoying giving back to the cause that has done so much for my family, my triathlon adventures provide me with a focus and physical outlet which is important in helping me come to terms with the loss of my daughter.

The next event I’m doing is a big one!

I am organising and part of a team that will be completing ‘Challenge Roth’ – a full-distance triathlon taking place in Bavaria next year. It’s an iconic race that involves a brutal 3.8km swim, 180km bike ride and a full marathon to finish! We will complete all of this, in theory, in under 15 hours – so it’s quite a challenge! Our team is made up of eight people who have never done a full-distance triathlon, a relay team and Dr Tamsin Lewis – a former Ironman UK Champion. We are being sponsored by some amazing brands including Trek Bikes, Athlete Lab, Challenge Tri Camps, Huub, Kat Berry Coaching and That Camera Man. Our objective is to raise at least £100,000 for use across all areas of the hospital. If we succeed, the total funds raised in Emma’s name will exceed £350,000.

I hope everybody’s incredible efforts and contributions will help ensure GOSH can do more research into the rarest diseases, support more families like ours and be able to treat every seriously ill child who needs its help. Emma would have liked that.

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FUNDING LIFE-CHANGING

PAEDIATRIC RESEARCH ACROSS THE UK For many seriously ill children, research is their only hope. Yet paediatric research is severely underfunded, receiving only 5% of the UK’s public and charitable funding for research each year.

In February 2017, Sparks, the children’s medical research charity, joined forces with Great Ormond Street Hospital Children’s Charity.

By merging national research funds, GOSH Charity and Sparks have allocated £2 million to a joint national call that invites researchers from across the UK to apply for funding for their innovative research to improve child health.

The call, which launched earlier this year, is the largest charitable call dedicated to child health research in the UK, and will benefit children at Great Ormond Street Hospital, nationally and around the world. Successful projects will be funded early next year after a rigorous process to ensure that only the highest quality research, with the biggest potential impact for seriously ill children, are supported.

The map to the right highlights some of the projects funded by GOSH Charity and Sparks charity, and shows the impact this type of research can have.

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FUNDED BY SPARKS

Smartphone technology to support speech therapy Newcastle, Dr Lindsay Pennington Cerebral palsy affects around one in every 400 children in the UK. The condition can cause difficulties controlling the movements needed for speech, which limits children’s social interactions and engagement. Dr Lindsay Pennington and her team are designing a new app that will allow parents and therapists to complete speech therapy sessions remotely.

It aims to work around busy family schedules and enable users to upload recordings, send messages and receive coaching from specialists. The smartphone app could also be used to help children and young people with other speech and language disorders.

FUNDED BY SPARKS

Bone-forming super gel for the treatment of cleft palates Birmingham, Dr Richard Shelton The operation for treating a child born with a severe cleft lip and palate involves taking bone from the child’s hip and transplanting it in the jaw. With any general anaesthetic, there is a risk of complications, and with surgery, there is always the risk of infection.

Dr Richard Shelton is developing a treatment in which a semi-solid gel, containing cells programmed to form bone tissue, is injected into the site of the cleft. This would be a much less invasive procedure and removes the need for complex surgery. Dr Shelton will test the technique in the laboratory before preparing it for use in the clinic.

FUNDED BY GOSH CHARITY

Kinder treatments for childhood cancer Glasgow, Professor Robert Mairs Every year, around 100 children in the UK are diagnosed with neuroblastoma, a cancer caused by cells leftover from a baby’s development in the womb. Current treatments such as chemotherapy and radiotherapy (high energy X-rays that kill cancer cells) can leave children with long-term side effects, including infertility and bowel and bladder issues. New treatments for neuroblastoma are desperately needed. Professor Mairs’ recent work has identified a new drug which, when used alongside radiotherapy, could be more a effective way of treating neuroblastoma. The drug improves the efficiency of radiotherapy, and may mean that lower doses can be used, reducing the side effects radiotherapy can have on surrounding tissue. This could prevent children having to live with the side effects into their adult lives.

FUNDED BY GOSH CHARITY (IN PARTNERSHIP WITH ACTION MEDICAL RESEARCH)

Learning and breaking habits to treat symptoms of Tourette’s Nottingham, Professor Georgina Jackson Undeliberate movements or vocalisations known as tics, are characteristic of Tourette’s syndrome. They usually begin as simple movements or sounds before the age of six, but progress into extended movements or words, peaking at around 10 years of age. Professor Jackson has designed an assessment that aims to improve the understanding of how tics develop and aid the design of strategies to manage the symptoms. Current behavioural therapies are based on the idea that tics are bad habits that need to be broken, but little is known about how children pick up habits or how they might unlearn them. The assessment will explore whether children with Tourette’s learn habits quicker than those without Tourette’s and retain them for longer, and might enable the team to improve treatment to prevent complex tics developing in adult life. This project was funded as part of GOSH Charity’s joint call with Action Medical Research.

FUNDED BY SPARKS

Preventing preterm labour with bioengineering London, Dr Tina Chowdhury Babies who are born too soon can develop issues that affect them for life, including learning difficulties and problems with sight and hearing. A major cause of premature birth is early rupture of the membranes that surround the baby in the womb. Once the membranes are damaged, they cannot be repaired, and this leaves both the mother and baby vulnerable to infection. Dr Tina Chowdhury and her team are engineering a membrane that could help heal the rupture, reducing the likelihood of infection and preterm labour, helping babies and mothers around the world.

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Sam with Amy now she has made a full recovery

A PARENT’S PERSPECTIVE

BY AMY AND MIA’S MUM, SAM 30 PIONEER

Amy (left) and Mia (right) enjoy dancing together at home

When giving birth to Amy, I needed an emergency caesarean, and when she was born she wasn’t breathing. I knew something was wrong because she didn’t cry, and I remember my husband, Darren, bursting into tears. The doctors were resuscitating her for eight and a half minutes.

Amy was floppy and couldn’t move anything but her eyes. She was taken straight to an incubator in the special care baby unit and kept in isolation for 24 hours while they did tests. I was scared to see her because I knew the reality would hit that we couldn’t take her home. You never think something like this will happen to your baby.

It’s such a shock.

At the time, we were told that Amy was unlikely to reach her first birthday and could remain completely paralysed. We were utterly crushed.

Our local hospital realised Amy needed specialist help and we were transferred to Great Ormond Street Hospital when Amy was four weeks old. I’d heard of GOSH as somewhere the most seriously ill children are treated – you never imagine your own child will have to go there.

But it’s only somewhere like GOSH that you can find a doctor who’s able to recognise a condition as rare as Amy’s. Amy was seen by Dr Adnan Manzur, who thought it might be chronic inflammatory demyelinating polyneuropathy (CIDP), an inflammatory disorder of the nervous system. We clung to hope that treatment might give Amy some movement, even if it just helped her move her arms. Throughout everything she had a little smile on her face and that gave us strength.

at home. I thought my eyes were playing tricks on me but then she did it again, just the slightest movement in her leg. I burst into tears.

On Christmas day, Amy took her first steps and it was the best Christmas present we could have hoped for. She was 15 months old.

After Christmas, we saw the nurses at GOSH and they were absolutely thrilled for us. We began to feel she could make a full recovery.

CIDP is more common in older children and it’s really rare for babies to be born with it. It’s also not genetic so, when I was pregnant, nobody expected our second child to be at risk…

Without the knowledge and expertise of the great doctors at GOSH, we might have lost Amy.

With our second little girl, Mia, it was very different. To hear her cry when she was born was absolutely amazing. They weighed her and then brought her over to me and it was everything you imagine it to be – it was perfect.

One of the happiest moments of my life was when Amy moved for the first time. She was six weeks old and it was during a physiotherapy session

But when Mia was a week old, I noticed that she couldn’t move her legs or feet at all. We went to a GP and then to our local hospital but,

We got Amy’s diagnosis about four months later and Dr Manzur was right – it was CIDP.

understandably, no-one had any experience of recognising CIDP. At three weeks old, Mia was referred to GOSH for tests, which showed that she had the same condition as Amy. We were fortunate that Mia’s condition wasn’t as severe as Amy’s, so as soon as Mia started treatment she began moving her legs again.

Now, Amy has made a full recovery and it looks like Mia will too.

Amy is at school and she’s interested in everything. She loves singing and dancing and doing little shows for us. She’s so energetic, and she’s constantly on the move. Mia’s just very cheeky.

One evening when we were in the hospital with Mia, Darren came up to the ward with all these leaflets from the fundraising desk in The Lagoon. He said that we owe our lives to GOSH and he wanted to do something to give back. I supported him 100%. The following day he signed up to Ride London and when our friends heard, they were inspired to sign up to a fundraising run.

When you have children at GOSH you want to do anything you can to support the charity. I can’t thank GOSH enough for what they have done for both our daughters. Without the specialists at GOSH, we might not have our little family. We will be forever thankful.

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Great Ormond Street Hospital Children’s Charity 40 Bernard Street London WC1N 1LE 020 3841 3131 gosh.org Great Ormond Street Hospital Children’s Charity. Registered charity no. 1160024.

Thank you to all the patients, families and staff who took part in creating this edition of Pioneer.

If you would like to stop receiving communications, you can contact us at any time at the address or telephone number on the left, or email supporter.care@gosh.org.