Pioneer - Winter 2022 edition

Great Ormond Street Hospital Children’s Charity

CALEB’S CHRISTMAS AT GOSH

Meet Caleb, who spent his first two Christmases in hospital

TRANSFORMING SIGHT AND SOUND

Inside GOSH’s lifechanging centre for sight and hearing loss

REVOLUTIONARY RESEARCH

GOSH Charity-funded projects that could change children’s lives

How GOSH Charity is helping paediatric health researchers bring their ideas to life.

A year on from its opening, Pioneer celebrates the impact the remarkable Sight and Sound Centre has had on the children and families who walk through its doors.

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WHY WE SUPPORT

A group of charities recently joined forces to provide a grant to GOSH Charity to fund a firstof-its-kind clinical trial – all for very personal reasons.

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When public health officials detected an increase in hepatitis cases in children in early 2022, they turned to an expert genomics team at GOSH to investigate why.

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Lily-May came to GOSH after being diagnosed with a brain tumour when she was a year old. Her parents, Lianna and Stephen, share their story with Pioneer

WELCOME

Welcome to the Winter 2022 issue of Pioneer and another edition packed full of inspiring stories showing the impact that Great Ormond Street Hospital Children’s Charity (GOSH Charity) and its supporters have on the children, young people and staff at Great Ormond Street Hospital (GOSH).

In this issue, we’re celebrating the magic of Christmas, and how GOSH Charity helps create a ‘home from home’ for children who are too poorly to leave the hospital during the festive season. This includes Caleb, who spent his second ever Christmas in surgery at GOSH, before having a heart transplant on New Year’s Eve. You can learn all about his story from page 12.

We’re also marking the first anniversary of the GOSH Sight and Sound Centre, supported by Premier Inn, which is the UK’s first dedicated medical facility for children with sight and hearing loss. From page 24, discover how the centre has been life changing for 17-year-old Paris and her family, as well as the GOSH staff who work there. There’s even a poem Paris penned specially for its opening.

GOSH is a place where the brightest minds come together to achieve pioneering medical breakthroughs that change the lives of thousands of children – and the world. In this issue, we speak with two researchers who are using GOSH Charity funding to develop much needed treatments (page 20) and share the story of a team of GOSH experts who were called on by the government to help solve a medical mystery (page 32).

Plus, we speak with Professor Helen Cross, who is the new Director of the UCL Great Ormond Street Institute of Child Health, to learn more about the institute’s mission to improve the health and wellbeing of children through world-class research (page 18).

Finally, it was with great sadness that we heard the news of the death of GOSH’s patron, Her Majesty Queen Elizabeth II, in September. The Queen had a long history with GOSH, and we are delighted to share some special moments and remember her wonderful contribution on page five.

I leave you now with this collection of personal and inspirational stories, which I hope will encourage you to continue supporting the incredible work that takes place both at GOSH and GOSH Charity.

Louise Parkes CEO Great Ormond Street Hospital Children’s Charity

On the front cover: Caleb, spent his second Christmas at GOSH.

IN REVIEW

STORIES FROM AROUND THE HOSPITAL AND CHARITY

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GOSH CHARITY IS THE 2023 TCS LONDON MARATHON CHARITY OF THE YEAR

We are excited to announce that Great Ormond Street Hospital Children’s Charity (GOSH Charity) is the official Charity of the Year for the 2023 TCS London Marathon!

GOSH Charity hopes to raise £3.5 million through the partnership and has launched its ‘Run it. Beat it.’ campaign to inspire runners and volunteers across the UK to join TeamGOSH and help beat childhood cancer.

Every week, around five children in the UK lose their lives to cancer. That’s five families who are faced with the worst news possible. For every child, parent and family – it’s time to beat it.

With fundraising support, the GOSH Charity team will help take the research, technology, facilities and

care Great Ormond Street Hospital (GOSH) delivers to the next level.

As well as recruiting runners for the in-person event, the charity hopes to inspire its supporters to take on the virtual TCS London Marathon, which returns for a fourth year in 2023.

TeamGOSH also plans to recruit hundreds of volunteers who will be at the heart of its community of supporters, cheering on those runners who are putting their best feet forward at the event on Sunday, 23 April 2023.

Together we can run it. Together we can help beat childhood cancer.

To learn more and to get involved, be it through running or volunteering, visit:

gosh.org/LondonMarathon

CELEBRATING 10 YEARS WITH PREMIER INN

Over the past decade, Premier Inn & Restaurants has provided invaluable support to GOSH Charity, helping transform the lives of seriously ill children across the UK.

In 2012, the company pledged to raise an amazing £7.5 million towards a new state-of-the-art space at GOSH, the Premier Inn Clinical Building. The opening of the building in 2018 enabled hundreds of children to be treated in brand new facilities, including new inpatient wards, operating theatres and a day care unit.

That same year, Premier Inn & Restaurants pledged to raise an additional £10 million in support of the Sight and Sound Centre. This incredible centre welcomed its first patients in June 2021 and is the UK’s first dedicated facility for children with sight and hearing loss (read more about it from page 24).

After a successful 10 years together, we are proud to say the partnership has been extended to allow this wonderful story to continue.

REMEMBERING HER MAJESTY QUEEN ELIZABETH II

It was with great sadness that GOSH Charity heard the news of the death of Her Majesty Queen Elizabeth II in September. The Queen had a long history with GOSH, and visited multiple times during her reign, including in 1952 during GOSH’s centenary celebrations (pictured).

She became Patron for the hospital in 1965 and officially opened the first purpose-built building for the Institute of Child Health the following year. She visited again in 1977 and then in 2002 to mark GOSH’s 150th birthday in the year of her Golden Jubilee.

Queen Elizabeth also attended events which fundraised for the hospital, including a Christmas performance of Peter Pan at the Barbican in 1982 and the memorial concert for Diana, Princess of Wales in December 1997.

It was in her role as Patron that she sent a letter of thanks to charitable supporters of GOSH following The Independent and London Evening Standard’s Give to GOSH appeal in 2015, which raised more than £3 million.

The letter, signed by ‘Elizabeth R’, said: “As one of the world’s leading children’s hospitals, Great Ormond Street offers a beacon of hope to thousands of children from across the UK and beyond every year.”

Earlier this year, GOSH Charity celebrated Her Majesty’s Platinum Jubilee as part of its ‘Play Street’ initiative, which saw Great Ormond Street closed to traffic and transformed into a play area on National Clean Air Day (16 June). Children, their families and the local community wrote messages of thanks and congratulations to Queen Elizabeth, which were hung on a special memory tree.

FAMILY GIVES £50 MILLION TO HELP BEAT CHILDHOOD CANCER

Founder and Chair of US-based private equity firm Lone Star, John Grayken, and his wife, international theatre producer Eilene Davidson Grayken, have donated an incredible £50 million to GOSH Charity to help build a new Children’s Cancer Centre (CCC).

The CCC will be a resource for children from across the UK and beyond with rare and difficult-to-treat cancers. Due to start construction in 2023, the centre will be designed with the needs of children

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and families at its heart and will bring all aspects of cancer care, from diagnosis to remission, under one roof.

The Grayken family, who previously gave £5.4 million towards the hospital’s iMRI suite, have a personal connection to GOSH, after Eilene’s nephew was treated at the hospital for a twisted bowel in 2010. Along with their generous donation, they will continue to support GOSH Charity’s work as cochairs of the CCC Campaign Board.

THIS TIME IN GOSH’S HISTORY

JM Barrie gave the copyright of his novel, Peter Pan, to GOSH in 1929. At Christmas time that year, the cast visited the hospital to perform scenes for the children, accompanied by James Barrie himself. Jean Forbes-Robertson was Peter, with Sir Gerald du Maurier (actor-manager and father of novelist Daphne du Maurier) playing Captain Hook.

I HAVE... A BRAIN TUMOUR

Rafe, 18, was diagnosed with a malignant high grade brain tumour when he was just four years old. Within five hours of his first MRI scan the family were referred to GOSH. Rafe shares his journey so far with Pioneer.

The only symptom I had initially was some vomiting in the morning, which had been happening for the previous three months. Then one afternoon, our lives were turned upside down when I was diagnosed with a malignant brain tumour.

That evening, I was admitted to Great Ormond Street Hospital (GOSH), and over the next 18 months I underwent six hours of brain surgery, had 33 rounds of radiotherapy under general anaesthetic and 15 months of chemotherapy.

I completed my cancer treatment in January 2010, but that wasn’t the end. I remain under six different specialities, I’ve had many operations on my eyes, and have a lot of medication due to the long-term effects of the treatment. I had to learn to walk again, with lots of physio, and I have left-sided weaknesses, which have improved after a long period of time.

If it wasn’t for the hospital and all the amazing work the staff do, I know that I wouldn’t be here now or be the person I am today.

MEMORIES OF GOSH

The first thing I remember when coming out of brain surgery was my reception schoolteacher being there with a massive toy fire engine with a remote control. I couldn’t walk at all, so she would guide me with it. There has never been one appointment that I haven’t wanted to go to at GOSH! It feels like we are part of a large family, as we’ve met so many staff over the years who were supportive during my visits. I particularly remember Mary, who was a volunteer in the Chaplaincy team, as well as Jim the Chaplain.

FUNDRAISING FOR GOSH CHARITY

GOSH has become a massive part of my life and I am passionate about raising money for Great Ormond Street Hospital Children’s Charity (GOSH Charity). The very first thing I did was a plant sale. It started off very small – I raised £9.50! But Helen, a lady who worked on the fundraising desk at the time, was so grateful and enthusiastic that it made me want to do more. So, I got a cheque out and wrote a big number on it as a goal, and that’s when it all kicked off.

Now I grow vegetables with my 75-year-old neighbour, Ronnie. We grow all sorts, from tomatoes to cucumbers. I’ve done it for quite a few years, and my mum and dad have even become my delivery drivers! We work as a

team – I do all the orders and they go and deliver them. There was one very generous couple who gave me £500 just for a few plants!

Fundraising for GOSH Charity is hugely important to me, as I’ve had so many MRI scans over the years, and I know this equipment costs a lot. I want to help give back. It’s reassuring to know that the money I’veraised is helping other children to get the support I had. I’ve raised over £20,000 in total, and I’m not going to give it up!

LIFE TODAY

Aside from fundraising, I love my animals. I have a chicken and a rabbit, and I’m an uncle to my brother’s cat. I love to cook, and my chicken lays an egg for me every day! We also belong to a sailing club, which I really love, and they asked if I would do the raffle this year and organise the prizes.

I have a placement working in a hospital and I’m hopefully going to be working in a pharmacy soon. I’m really interested in working with children, and I’ve completed courses in childcare and health and social care. With this illness I’ve realised that life is precious, so I should grab it every day.

Right now, I’m in the process of transitioning into adult care. It’s been very backwards and forwards, so I don’t think we quite realised it was the final visit at GOSH until we got there, which was probably a good thing. We hadn’t realised because for us, GOSH is part of our lives, part of our family. And I know that the doors are always open.

THANK YOU TO GOSH

I am very proud and forever grateful to GOSH. If it wasn’t for the hospital and all the amazing work the staff do, I know that I wouldn’t be here now or be the person I am today. That’s the reality. From the doctors and nurses who have been there from the very start to those who have visited me on the wards, I’d like to say a massive thank you to them all.

To other children just starting on their journey at GOSH, I want to say that it may seem like a big, scary place, but it’s not. It’s a friendly, homely place, and the staff there are like a second family to me. I know GOSH’s motto is that every child matters. And from my experience that motto is totally lived out.

There has never been one appointment that I haven’t wanted to go to at GOSH. It feels like we are part of a large family.

TULSI’S TIME AT GOSH

While she was developing inside the womb, Tulsi developed spina bifida – a defect that stopped her spinal cord from forming properly. She was left with a hole in her spine and a sack of spinal fluid exposed on her back. Mum Laxmi shares her story.

Tulsi was diagnosed at our local hospital at my 20 week scan. It was an emotional moment; I hadn’t even heard of spina bifida before. As a mother it was so difficult, we were told our baby girl might be paralysed, need a tube in her brain to relieve pressure or, worse, not survive.

Every time we had a scan, the lump on her back got worse. It was scary, and I tried to learn more about the condition and picture what life might be like for her.

As Tulsi grew, we found out that her right foot and the nerves in her legs weren’t developing properly, and the lump on her back was getting bigger. But we made sure to focus on the positives. Our spirituality gave us strength, and our brilliant consultant was determined to get the best care for our baby when he arranged a referral to Great Ormond Street Hospital (GOSH).

We first came to GOSH while I was still pregnant. We met a spina bifida specialist named Dr Tahir, who told us Tulsi’s best chance at life was to have delicate spinal surgery within hours of being born.

He walked us through what would happen, but I couldn’t follow what he was saying. All I could think about was how fragile Tulsi would be.

When I was eight months pregnant, we had an MRI scan that gave us a bit of hope. It was so amazing – the scan showed that Tulsi was kicking inside me. Having been convinced that my baby would be paralysed from the waist down, it was such a positive sign to see her moving around.

LIFE-CHANGING SURGERY AT GOSH

Tulsi was born at our local hospital in Northwick Park in Harrow and then taken to GOSH for treatment. When she was born, we had to be so careful, we couldn’t hold her.

At just a day old, she had eight hours of surgery. After two days, we were finally able to hold our new baby girl. We had the best doctors looking after her and they saved my daughter’s life.

She recovered in hospital for two months, and during that time I barely left her side. The doctors and nurses at GOSH were so supportive, encouraging me to take care of myself so I could care for Tulsi. I wasn’t sleeping in the hospital, and I wasn’t coping. The nurses made sure I had a room to rest in and insisted I got a good night’s sleep, which gave me enough energy to get through until Tulsi could come home.

Unfortunately, not long after returning home, Tulsi’s wound became infected, and we were back to square one. She needed to return to GOSH for a second operation.

While I was alone with Tulsi at GOSH, my husband visited us every day and our other two children, Radhika and Paarth, came twice during their summer holidays. It was nice for them to see their baby sister, but I didn’t want them spending too much time in hospital. It wasn’t easy being away from my family; it was heart-breaking not being able to be in two places at once.

Tulsi had spinal surgery at GOSH within hours of being born.

BEATING THE ODDS

After recovering from her infection, Tulsi has gone on to thrive. She’s five now and loves school. She is a burst of energy. She’s so strong, and it’s been remarkable to see her overcome so much trauma.

For a few years she went back to GOSH every couple of months for a check-up, and the doctors still keep an eye on her back, brain and bladder. We know she’ll face challenges, but we’re not focusing on the negatives. We see her for who she is, and not for her physical difficulties.

This summer we took her for a day out without her pushchair. We usually take it everywhere in case she gets tired and needs a rest, but we went to a theme park and she managed the whole day walking and playing. Her health has been amazing. She does everything that her brother and sister do and as parents we treat them all the same.

We call Tulsi our miracle baby; she has beaten the odds. We take comfort in the fact that she’s in the very best hands at GOSH. There are no words to describe the consultants, they are world leading.

A NEW TREATMENT

It’s incredible what these doctors can do, and science moves on all the time. Now there is a new option for parents facing a diagnosis like ours – a new spina bifida surgery at GOSH that repairs the baby’s spine while still in the womb. It’s just fantastic. It gives families another treatment choice, which is so important.

The biggest thing we must think about is changing her catheter every three hours and keeping infections at bay, but it’s part of our routine now. You wouldn’t know there was anything wrong with her, although she has to use more energy than other children to keep up. We spot the signs when she is getting unwell and know what to do.

When you’re receiving so much bad news, it’s really encouraging to hear that with surgery, your baby will survive, that they’ll smile, have their own unique personality, maybe walk and lead a near enough normal life.

We have spoken to other parents expecting children with spina bifida, an opportunity that we ourselves did not have, and shared Tulsi’s story. It has given them hope. Parents can rest assured that their children will get the best treatment and care in the land from the medical staff at GOSH.

The doctors and nurses at GOSH were so supportive, encouraging me to take care of myself so I could care for Tulsi.

NEW SURGERY BREAKTHROUGH

A team from Great Ormond Street Hospital (GOSH) recently became some of the first to carry out pioneering surgery to repair the damaged spinal cords of babies in the womb.

Dozens of babies with spina bifida have so far been spared paralysis and other life-limiting conditions thanks to the breakthrough treatment.

Babies with spina bifida have gaps in their spines where the spinal cord and surrounding vertebra don’t form properly. This can cause changes in the brain, as well as severe injuries to the nerves.

The new surgery requires an experienced, multidisciplinary team, and involves exposing the foetus while the mother is under anaesthetic – similar to a Caesarean section. The neurosurgeon cuts around the exposed spinal cord, which is protruding through

a hole in the back. After putting the spinal cord back into the spinal canal, a protective tube of muscles and skin is created around it to prevent spinal fluid from leaking.

“Closure in the womb is an alternative to postnatal surgery and improves short- and medium-term outcomes,” GOSH lead neurosurgeon Dominic Thompson says. “While neither intervention is fully curative, in foetal surgery, the defect is closed earlier, which prevents damage to the spinal cord in the last third of pregnancy.”

The surgery is available in the UK thanks to charitable funding totalling £450,000 from Great Ormond Street Hospital Children’s Charity (GOSH Charity) and University College London Hospitals Charity. The funds facilitated research and provided training for the surgical team through collaboration with colleagues at KU Leuven in Belgium.

It will give babies a significantly better chance in life, as people with spina bifida are very often incapable of walking and may require a series of operations to drain fluid from the brain (known as a shunt placement) later in life.

The National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, the NIHR Great Ormond Street Hospital Biomedical Research Centre and UCL Great Ormond Street Institute of Child Health (ICH) are also supporting the research.

“The groundbreaking work … wouldn’t be possible without funding from GOSH Charity,” Dominic Thompson says.

“For many children treated at GOSH, research offers them hope. Thanks to many generous supporters, GOSH Charity is now the largest dedicated funder of paediatric research in the UK, investing funds to help discover new treatments and cures for children with complex and rare conditions.”

For many children treated at GOSH, research offers them hope. Thanks to many generous supporters, GOSH Charity is now the largest dedicated funder of paediatric research in the UK.

A HOME FROM HOME AT CHRISTMAS

For the children whose treatment needs to continue over the festive season, the staff at GOSH do their best to make it as magical as possible. This includes Caleb, who spent his second ever Christmas in surgery, before having a heart transplant on New Year’s Eve.

He was just a day old when doctors discovered Caleb had a heart murmur, low oxygen and three holes in his heart. After a few nights in his local hospital in Abergavenny, Wales, Caleb was discharged, and his parents were told everything was fine. Then, at around nine weeks old, he had a cardiac arrest at home.

“It was quite unbelievable that he survived it, because it was so severe,” Caleb’s mum, Jenna, says. “It was after this that we found out he had cardiomyopathy [a disease of the heart muscle].”

In the months following, Caleb was in and out of hospital, including a blue-light trip to Bristol Hospital where he was fitted with an emergency pacemaker.

‘‘Every time Caleb picked up a common cold, it would be really dangerous for him,” Jenna says.

“Our visits to hospital became more and more frequent. They went from being every few months to every couple of weeks and we just knew his heart wasn’t going to get better.”

ARRIVING AT GOSH

In June 2021, two days before his first birthday, Caleb became very poorly and was taken to Cardiff Hospital in an ambulance, where doctors had to ventilate him. It was clear that he would need a heart transplant, so Caleb’s doctors got in touch with Great Ormond Street Hospital (GOSH) for advice.

“We arrived at GOSH in the early hours of the next day and Caleb was taken straight to intensive care as an ECMO [a machine that acts in place of a child’s heart and/or lungs] patient,” Jenna says.

“The Monday was Caleb’s first birthday, so it was really hard being in hospital for that, with him being on a ventilator. We had to sing ‘Happy Birthday’ on

FaceTime with his older brother and sisters, which was tough.”

The family was told there were two choices: doctors could fit Caleb with a new pacemaker, or he could be put on a Berlin Heart, which is a mechanical device used to support children in severe heart failure, either until recovery or until a heart transplant is possible.

“We decided to take the chance to put Caleb on the Berlin Heart, so on Wednesday he went into surgery for nine hours, which went well,” Jenna says. “After the surgery, he spent five weeks in intensive care and was on a ventilator for 19 days.”

LIFE ON BEAR WARD

Caleb was eventually well enough to transfer to Bear Ward, where he spent seven-and-a-half months. He grew stronger and enjoyed visits from the Play team, which is funded by Great Ormond Street Hospital Children’s Charity (GOSH Charity).

“The Play team were amazing with Caleb.” Jenna says. “They did lots of arts and crafts and painting with him, which he loved. We also had music therapy every week, where someone would come in playing guitar and we’d all sing together. It helped so much – it broke the day up and stopped Caleb getting bored.”

Meanwhile, Caleb’s dad, Jamie, and Jenna spent alternate weeks in the hospital and at home with their other children. They stayed in GOSH Charity-funded family accommodation, where Jenna says they had the support of other families going through similarly challenging experiences.

“We would see each other every week for about five minutes, have a quick hug and then go our separate ways,” Jenna says. “It sometimes got quite lonely.

“But thank God for the other families we met, they really helped us along the way. We met two families who were on the Berlin Heart at the same time as us, as well as other families on Bear Ward and in the accommodation, which was lovely.”

AN ANXIOUS WAIT

Although everything seemed to be going well, one day Caleb lost movement in his right side. He was taken for a CT scan, and Jenna rushed back to London from their home in Wales to be with him and Jamie. The scan revealed Caleb had had two strokes, with a second scan later showing a third stroke on the opposite side of his brain.

“We were taken back down to intensive care. We were told that it was so severe, it was basically life or death and we had to take it hour by hour,” Jenna says.

“We asked if we should bring our other kids in, just in case, and they said yes as they didn’t know what was going to happen. They said the chances of him waking up were quite slim.”

Over the next 24 hours, Caleb had numerous short seizures as his parents waited anxiously to see what would happen.

“Then our kids came in and it’s almost like Caleb turned a corner once he heard their voices. He got through

that night and within a day or two, he was back watching his tablet and giggling,” Jenna says.

“Within a week, we went out of the cubicle and back into the bay where he went on to recover from his stroke. He had physio and occupational therapy every day – it was intense but then we got transferred back upstairs to Bear, which was amazing.”

CHRISTMAS AT GOSH

Unfortunately, on Christmas morning, Caleb had to go into surgery again. It was a stressful time for his family, but Jenna says they tried to make the most of it.

“We managed to have a cubicle and the family all came to the hospital to have Christmas Day together, and we were able to spend Boxing Day together, too,” she says.

“As Caleb was on a Berlin Heart and it was in the middle of COVID, we weren’t allowed on the bay, but we spent time together in the sensory room and on the landing so the kids could see Caleb.”

Being in hospital over Christmas was “a lot better than we thought,” Jenna says, thanks to the staff who go above and beyond to bring magic to the wards.

“Father Christmas visited, and we decorated our bay. They gave us Christmas dinner in the canteen, which we ate together while Caleb was in surgery. The staff brought so many presents round for Caleb and they made everyone feel so welcome.

“The idea of spending Christmas in hospital was really daunting, but it was actually a really lovely day. All the staff were so kind … We had a room together, so we did presents and played some games.”

On New Year’s Eve, the family got the news they had been waiting for: a donor heart was available. Caleb went into surgery that night.

“To be in surgery on Christmas Day and then New Year’s Eve for two completely different things was just crazy – everything happened very quickly,” Jenna says. “While Caleb was in surgery, we went onto the hospital rooftop to watch the fireworks at midnight, which was so peculiar, but it was almost perfect.”

After a successful surgery, Caleb recovered in intensive care for a few weeks before returning to Bear Ward. He was discharged at the end of January 2022.

The idea of spending Christmas in hospital was daunting, but it was actually a really lovely day. All the staff were so kind.

BRINGING FESTIVE FUN

For most children, Christmas morning is about the excitement of waking up to see what Father Christmas has left and playing with their new toys and games. Thanks to the wonderful Play team, the experience for children at Great Ormond Street Hospital (GOSH) is no different.

Funded by Great Ormond Street Hospital Children’s Charity (GOSH Charity), the job of play workers and specialists is to bring fun into the hospital, while helping to ease children’s fears and concerns. At Christmastime, the team also works hard to make GOSH feel like a true ‘home from home’ for those too poorly to leave the hospital.

Kimberley Millar, a Play worker on Bear and Flamingo wards, says Christmas in the hospital is her favourite time of year.

“The whole experience at GOSH is very magical over Christmas,” she says. “We work with the children and families to create decorations, we put up lights and play festive music to help get everybody in the festive spirit. I find it really rewarding working over Christmas at GOSH … I really enjoy putting lots of smiles on everyone’s faces.”

The Play team starts getting ready for Christmas in October, ordering supplies so they can decorate at the beginning of December – provided there are no infections on the ward which would stop this from happening.

“There's an elf – like Elf on the Shelf – who goes to different wards to play, get up to mischief and to have fun,” Kimberley says. “The Play team works with the children to create handmade decorations to decorate the ward and their bed space or cubicle. It’s important to include patients and families as it’s a time to be joyful and festive, and by decorating the ward it builds up the spirit and excitement.

“We also work with GOSH Charity to collect donations of toys, books and games, which we wrap up. On Christmas morning, the children all wake up with sacks at the end of their bed or cot, which are made by the Play team. We have a visit from Father Christmas and Disney characters, who we take round to see all the children, which brings lots of Christmas spirit. We also provide lots of Christmas activities for children and families to do.”

CREATING CHRISTMAS MAGIC

For Senior Chaplain Dorothy Moore Brooks, working at Great Ormond Street Hospital (GOSH) over the Christmas period is “a privilege and a blessing”.

The multi-faith Chaplaincy team, which is funded by Great Ormond Street Hospital Children’s Charity (GOSH Charity), supports families through some of the hardest moments, offering a listening ear and providing solace to patients and parents of all faiths and none.

“We celebrate many major festivals from different traditions throughout the year, and Christmas is no different,” Dorothy says. “But the Christmas story has a special poignancy in a children’s hospital because it’s all about a family who were far away from home, facing an uncertain future.

“GOSH, on Christmas Eve, encapsulates that stable scene for me. The team hosts a carol service and midnight Mass ... The chapel is full of people of all faiths; staff come down between shifts and families too. We come together as one extended family. There is something magical about being in the candlelit chapel, and everyone standing with hope in their hearts for the children.”

Everyone helps to bring Christmas magic into the hospital, with decorations, festive activities, a special Christmas lunch and gifts provided by GOSH Charity to open on Christmas Day.

"Christmas is always a really special time of year at GOSH,” Dorothy says. “Everyone, both at the hospital and charity, goes to such lengths to try to make sure the children being treated over the festive season have a special time. It’s about making it feel as much like home as possible.”

THE PIONEER INTERVIEW

Professor Helen Cross, Director of the UCL Great Ormond Street Institute of Child Health, speaks to Pioneer about her world-leading work in epilepsy and how support from GOSH Charity will help drive the institute forward.

Did you always want to pursue medicine?

Yes, I was one of those children who really wanted to do medicine from a very early age! And as soon as I did paediatrics it was quite clear that’s what I wanted to specialise in.

Children are so much fun. They deal with illness in such a special way – they are a real joy to look after. It’s also a privilege to be involved in the care of individuals so early in their life.

How did you come to focus on epilepsy?

When I arrived at Great Ormond Street Hospital (GOSH) in 1990 to do my paediatric neurology training, by sheer coincidence the first clinical MRI scanner for children had just been installed. It was an absolutely amazing opportunity to look at the brain in a way we had never been able to before.

What impact does epilepsy have on a child’s life?

Epilepsy is a condition whereby an individual is prone to recurrent epileptic seizures, a change in movement or behaviour, which is the direct result of a change in the electrical activity of the brain. Seizures are spontaneous and unpredictable in the majority of cases, and may take a variety of different forms, whether it be a child falling to the ground and convulsing, or a change in behaviour and awareness.

So there are many different types of seizures, and if they’re uncontrolled, they really disrupt life. Many of the kids with early onset epilepsy have associated neurodevelopmental and behaviour problems, which means they may not progress in the same way as their peers. These impacts can be greater than the seizures themselves.

How has epilepsy care and treatment developed?

We’re better at describing the different types of epilepsy, and then finding the different causes, which has given us an understanding of ways forward in management. We’re not there yet in gaining a cure, but certainly in surgical cases we can do so, which we couldn’t do before.

You started as Director of the UCL Great Ormond Street Institute of Child Health (ICH) in September. Why did you want to take on the role?

The institute is an amazing place. It’s an honour and a privilege to have been given the post. The research we do here is incredible – together, ICH and GOSH form the largest concentration of children’s health research in Europe. It’s already in a great place, so my main aim is to maintain and further develop ICH in its relationships across UCL, nationally and internationally.

What impact does Great Ormond Street Hospital Children’s Charity (GOSH Charity) have on the ICH?

The charity is extremely important. We all have the same aim in trying to further the care of children, particularly with rare disease, and we are in a fantastic position with having the research that goes on within the university, which the charity helps fund, translating into clinical practice across the hospital.

FUNDING VITAL RESEARCH

At the UCL Great Ormond Street Institute of Child Health (ICH), hundreds of researchers work on projects that could lead to new ways to diagnose, monitor, treat and cure childhood diseases.

The ICH is the primary research partner of Great Ormond Street Hospital (GOSH), with research from the institute often leading to clinical trials in the hospital and real benefit for the children.

A recent research project included a study into the brains of children with epilepsy, which will help pave the way for improved surgical treatment of the condition. Lewis-Spitz Surgical Scientist Aswin Chari, whose role is funded by Great Ormond Street Hospital Children’s Charity (GOSH Charity), led the team carrying out the research.

Why is GOSH such a special place?

It is a place where many families come almost as a last resort, and we are able to achieve such a lot. Everything we do is for the children, and we work as a team. No matter how complex the problem we have in front of us, we set out to achieve a resolution.

What has been most satisfying in your career so far?

Along with William Harkness, I developed an epilepsy surgery program at GOSH, starting in 1992. It became one of the biggest in Europe, if not the world, but we couldn’t do it all. In 2012, we achieved a centralised service, with four locations in England. This tripled the number of kids being evaluated and operated on with good outcomes.

I have also been closely involved with the development of the National Institute for Health and Care Excellence guidelines on diagnosis and management of epilepsies. I think they have really turned around care for people with epilepsy in the UK and I remain very proud to have worked on them.

How do you spend your time outside of work?

I have a husband and three daughters who are now in their 20s, and I try and spend as much time with them as I can. My husband would say my work is my hobby!

“We used diffusion MRI technology to teach us about the function of children’s brains, helping to deepen our understanding of debilitating conditions like epilepsy,” he says.

“Although surgery for epilepsy is relatively safe, it is a large undertaking and there are some children who undergo surgery but sadly continue to have seizures.

“We hope that through this technology and analysis, we can enable more children with the condition to benefit from life-changing surgery and treatment.”

FROM CONCEPT

TO CREATION

How GOSH Charity is helping paediatric health researchers bring their ideas to life.

Every year, Great Ormond Street Hospital Children’s Charity (GOSH Charity) invites researchers from across the UK to apply for funding for child health research projects through the GOSH Charity and Sparks National Call.

This is the UK’s largest charitable grant making scheme dedicated to paediatric rare disease research and aims to support researchers working across a range of medical conditions.

Pioneer meets two researchers who received grants via the National Call in recent years to find out how the funding is making a difference.

PROFESSOR PATRIZIA FERRETTI, UCL GREAT ORMOND STREET INSTITUTE OF CHILD HEALTH

Grant awarded to generate human models of a rare condition called acrodysostosis. Some of the symptoms associated with acrodysostosis can include skeletal malformations and intellectual disability.

How would you explain your project to someone who isn’t a researcher?

We’re looking at a set of diseases called acrodysostosis. They are very rare, which means they’re more difficult to study. However, the genes that cause the disease have been identified.

Through this project, we want to understand what causes the different symptoms associated with these diseases, and how we can help improve them. At present, the effects of these diseases are managed but not cured.

In a type of this disease called acrodysostosis type 1, the main issues we find are skeletal malformations.

These are shared by and large with acrodysostosis type 2 – but there are some symptoms that are different in these two diseases.

In type 1, we see a lack of responsiveness towards hormones – for example, growth hormones, which can result in short stature – but the cognitive level is usually normal. In contrast, with type 2, the response to hormones is normal, but children can have cognitive problems, so there is also involvement with the brain. What we’re trying to disentangle is: what is the basis of these differences?

To try and find out, we are looking at cells that are derived either from patients or generated by us – with some modifications to mimic the disease – focusing on cells that make cartilage and bone, and neural tissue.

Will understanding the diseases lead to better treatments?

Yes. By establishing models, which are currently lacking, we can start to look at which components of the pathway are not working at a molecular level. It will also help us understand what might be causing deficits in cartilage and [the] nervous system.

For example, if we have patient cells in a dish that are going to make cartilage and prematurely turn into bone, we want to stop that. So, if we can understand the key steps leading to that happening, we can start thinking of ways of interfering with it and restoring normal growth at the joints. The hope is that this will eventually translate into therapy for affected patients.

How far into the project are you?

We’re only a year into the grant. Certain things are moving a bit slower than we’d like, some things are going according to plan. But that’s science. The solution will not be immediate, but the idea of starting to test some promising therapeutic compounds on the model we are building is really very exciting.

What’s been the best thing about the project so far?

Having contact with patients and families. Also, starting to build up a network with other colleagues, so that together we can do more for children with this disease and related diseases. It’s a very good feeling, that there is progress being made.

Why is the National Call important?

I think it’s crucial. The National Call is a good starting point for many projects focusing on rare diseases. It also encourages a lot of interaction between researchers and clinicians. What we’re doing is not simply curiosity driven – we want to connect with relevant clinical colleagues, so we can do things that will really benefit patients.

I also think supporting paediatric research is very important. Some of these diseases might not be absolutely life-threatening, but they have such an impact on individual children and their families. These children have long lives ahead of them. You really want people to have a good quality of life. We care a lot about that.

DR HASSAN RASHIDI, UCL GREAT ORMOND STREET INSTITUTE OF CHILD HEALTH

Grant awarded to develop an implantable and removable ‘liver patch’, providing liver support to patients with the rare metabolic condition non-ketotic hyperglycinemia.

Can you tell us about your project?

My research is focused on developing new ways for patients to receive treatment for liver disease. Currently, a liver transplant is the only treatment for inborn liver disease and liver failure. While saving many lives, there are a lot of limitations associated with the procedure, such as needing to find a perfect match in terms of immunologic markers, and needing immunosuppression treatment, which can cause problems in the long term. Liver transplantation is also a major, high-risk surgery, particularly for babies and children.

I am developing a liver patch which will either allow patients to avoid liver transplantation altogether or will bridge them to another form of treatment.

Who are the patches for?

In principle, the patch can provide liver support for a wide range of liver insufficiencies, including babies born with rare metabolic disorders and patients with acute liver failure and chronic liver disease.

However, we’re initially testing it on a condition called non-ketotic hyperglycinemia, which is where one of the enzymes involved in breaking down a small molecule called glycine is not functional. Glycine is one of the amino acids, which are the building blocks of proteins.

Amino acids are initially broken down by the liver and then excreted from the body. If this doesn’t happen, they accumulate in the blood and become toxic. In nonketotic hyperglycinemia, glycine doesn’t break down completely. This causes a lot of issues for children with this rare disorder, such as severe epilepsy, and there is no effective therapy.

Researchers at University College London (UCL) are also working on gene therapy treatments for infants with this condition. We hope the liver patch will be beneficial during the early stages of life, either as an additional treatment alongside gene therapy or as a supportive treatment until gene therapy can be used. In other conditions, we see the liver patch sustaining a child until they’re old enough to receive a transplant or gene therapy, if available.

How do the patches work?

You can think of them as similar to a teabag, but instead of tea leaves they contain liver cells, which we can generate in the lab. These cells act as a secondary liver and provide enough support to treat certain conditions.

We don’t transplant the patch into the liver. We can transplant it at an accessible site, such as under the skin of the belly, which is a more straightforward and less risky surgical procedure. And we’re developing the patch in a way that means immunosuppression treatment won’t be required.

Our liver patch has two main compartments. One is a capsule made from a material that is already approved for clinical applications. The main function of this is to contain transplanted cells in a single location, so instead of spreading throughout the patient’s body, the transplanted cells remain inside the enclosed patch and can be easily removed or replaced.

The second compartment is the cells, which are enclosed in a layer of gel. We generate these cells from pluripotent stem cells. This is a type of stem cell that can become any cell type in the body. In principle, we can propagate them indefinitely, so we can make billions of cells from them.

The gel keeps the cells hidden from the immune system while they function as liver cells. This means the transplanted cells won’t be detected as a foreign object by the immune system of the person who received them.

We can make these cells in advance and freeze them, so they can be transported and stored easily. When needed, the cells can be defrosted, loaded onto the patch, and transplanted to patients without wasting valuable time.

How is your project progressing?

Tremendous progress has been made. We’ve come up with novel methods for making the patch and covering the cells in the gel, which we hope to patent. The most important thing is that the cells actually do function and break down glycine inside the body. In theory they should, but we need to show that happening in practice. This part of the work is currently in progress.

After that, we’re hoping to secure more funding, because we’re currently operating on a very small scale. We need to show that we can mass produce the cells and generate several million or even billions to meet the demand. While early safety tests show that these cells are safe, we also need to test their long-term safety and functionality before taking it to clinical trial.

What would you say to GOSH Charity donors?

The grant was secured in collaboration with Professor Nicholas Greene, a fellow researcher at UCL Great Ormond Street Institute of Child Health, who is studying several metabolic conditions, with a particular focus on non-ketotic hyperglycinemia. I personally am very grateful to GOSH Charity for the funding and to donors for their generous support. It has helped take this liver patch from a concept to an early prototype and to test its therapeutic efficacy and function.

A CENTRE OF TRANSFORMATION

The Great Ormond Street Hospital (GOSH) Sight and Sound Centre, supported by Premier Inn, is the UK’s first dedicated medical facility for children with sight and hearing loss. Partly funded by Great Ormond Street Hospital Children’s Charity (GOSH Charity), the centre features state-of-the-art soundproofed booths for hearing tests, an eye imaging suite, a dispensing opticians and other testing facilities. There is also a sensory garden with plants that children can see, touch, smell and hear, and bespoke and engaging artworks commissioned for children and young people with sensory loss.

One of those young people is 17-year-old Paris. Born prematurely at just 24 weeks and weighing less than a pound, Paris was severely deaf in one ear and profoundly deaf in the other. In 2017, aged 13, she woke up one morning with no hearing at all, and was referred to GOSH, where she received a cochlear implant.

The upgraded facilities play a crucial role in the hospital staff’s ability to provide extraordinary care and expertise, as well as helping children and young people with sensory loss feel comfortable in their surroundings.

“There’s no noisy corridor, no travelling down to the darker and colder basement for hearing tests, no crowded rooms,” Paris says. “In the new facilities, the waiting rooms are much smaller, which is nice because they are quieter.”

Having spent five years at GOSH, Paris has experienced the old sight and sound facilities as well as the new centre.

“My first experience at the Sight and Sound Centre was amazing!” she says. “All the specialists are there for you in one building. And it’s easier going into an appointment, because it’s a lot calmer. That’s the biggest impact.”

Paris’ mum Tricia says the centre’s impact extends beyond the children who are there for treatment. “The staff are working in a nicer environment, so they are a lot happier, and you see that,” she says. “And families can now go through an easier process due to having a place that is specifically designed for them. I can’t even put the words together to describe how much of an impact it’s had on us as a family.”

A year on from its opening, Pioneer celebrates the impact the remarkable Sight and Sound Centre has had on the children and families who walk through its doors.

My first experience at the Sight and Sound Centre was amazing! It was so different, the atmosphere was immediately more relaxed, and I knew it was much better from the first moment in there.

The Sight and Sound Centre opened in 2021

A SENSORY EXPERIENCE

Children with sight and hearing loss were involved in designing the centre, and artworks with sensory elements are featured throughout.

“I love the sensory garden,” Paris says. “It’s really pretty, and it’s nice to have a space where you can go outside and are able to be quiet. I never used to have that.”

“I’ve explained to others in the deaf community what the Sight and Sound Centre provides, and they are totally amazed, because they can see what Paris has achieved,” Tricia adds. “They can see how she has been supported. And they know the struggles deaf children go through, so to have a centre specifically designed for them is world class. To invest in more facilities like these is critical.”

In her spare time, Paris loves listening to music and going to festivals, and she writes her own lyrics and poetry. She even wrote a special poem for the Sight and Sound Centre, which she read at its opening (see page 27).

“There’s a comfortable feeling of knowing the centre is there, of knowing it’s open,” she says.

With Paris about to transition into adult care, Tricia reflects on the past year in the Sight and Sound Centre, and how she feels about moving forward.

Paris was recently included in the 2022 Young Leaders Directory, in partnership with International Day of the Girl. “That’s because of what she’s done for deaf awareness,” Tricia says. “But equally, the hospital and GOSH Charity have helped to give Paris the platform to use her creativity. There aren’t many places you can go as a parent of a disabled child where you’re going to get that empowerment. That’s why donors need to fund GOSH Charity, because those kids come out of GOSH with abilities they might not get elsewhere.”

EACH YEAR AT THE SIGHT AND SOUND CENTRE...

7000 ophthalmology patients visit the centre.

3500 children are treated by the Ear, Nose and Throat (ENT) team.

1500 children are treated by Speech and Language Therapy specialists.

600 children are treated for cochlear implants.

Organ pipes play

families climb and descend the centre’s spiral staircase

Source: based on known data for 2019/20 financial year. All figures are approximate.

Top: the sensory garden has plants for children to see, touch, smell and hear. Bottom: artwork features throughout the centre.

GOSH patient Paris and her mum, Tricia

Consultant Paediatric Ophthalmologist

and Vitreoretinal Surgeon Robert Henderson has worked at GOSH since 2014. He shares how the new facilities at the Sight and Sound Centre have changed patient care for the better.

“The Sight and Sound Centre is a wonderful space. It’s given us room to breathe and to expand. Previously, we were in the Frontage Building, where we had a single long corridor.

“Parents couldn’t sit without dodging one another’s strollers. The new centre is much more comfortable. It’s quieter, we’re split over a number of floors, and you have that beautiful atrium with the organ pipes running through the middle of it.

“We have new cutting-edge equipment and having the two prominent senses co-located in the same building makes a lot of sense. Our Eye Clinic Liaison Officer now has her own room for talking to patients, our Genetic Counsellor has her own counselling room. We have a dedicated imaging room, helping to completely revolutionise how we examine patients’ eyes.

“The sensory garden is wonderful. It’s just outside my room, and it’s lovely to be able to walk outside

Head of Nursing and Patient Experience

in the Sight and Sound Directorate, Carolyn Akyil has been at GOSH for 31 years. She tells Pioneer how the new centre has made a huge difference to her team and the families they support.

“I’ve worked at GOSH basically all my adult life. The changes that we've seen over that length of time have been quite staggering, but one of the biggest has been that of sight and sound.

“The Sight and Sound Centre has been specifically designed to meet the needs of the patients. From signage created with the children in mind, to the way the rooms are laid out and the equipment within them. You can’t beat that.

“Distance is important in some eye tests. In the old facilities, the team had to add a note to the patient’s record to say which room they’d tested in, as nothing was standard. In the new rooms, they all have capacity for testing at the appropriate distance. The labs have been custom built with great equipment, and we also have an optician where children can choose their glasses, as well as facilities for glasses and hearing aid repairs.

and find the kids playing, or just to sit there quietly with a bite of lunch. I’m a beekeeper, it’s a hobby of mine, and in midsummer all the bees come into the garden. It’s amazing.

“All these things wouldn’t have been possible without some extraordinary donations from our benefactors, so we are hugely grateful to the charity and the donors, including Premier Inn. Without them, we wouldn’t be able to bring a lot of treatments to our patients. It’s so important to continue to renovate, to allow us to innovate. And that applies whether it’s oncology, cardiology or neurology – we all need facilities we can be hugely proud of.”

“It’s light, it’s bright, it has high ceilings. There’s a seminar room so staff can hold meetings and learn from one another, with great AV equipment to help our teams work together. The old chapel has been converted into a beautiful coffee room and breakout space. It’s so important to have these things, because if you look after yourself you can look after the patients better.

“I’ve been involved in showing some of the supporters around and it’s lovely to see it again through their eyes, to see how proud they are of what we’ve been able to achieve. We have the best people here. And having the best facilities to go with that is what our patients deserve.”

A poem for the Sight and Sound Centre

For Sight and Sound, mild, moderate, severe, profound is all to be found. Right here.

Are you crossing your fingers with a sigh, because you’ve been here before? But now, with a feeling you can’t describe you realise what it all was for.

Is it swirling around your mind? Watch it float away on the wings of a butterfly and watch the people around go all-in for you.

For Sight and Sound mild, moderate, severe, profound. Look what we found. Right here.

by Paris Thompson

WHY WE SUPPORT THE CHARITY

Diffuse midline glioma is an aggressive type of brain tumour that kills most children within two years of diagnosis. A group of charities recently joined forces to provide a £1.2 million grant to GOSH Charity to fund a first-of-its-kind clinical trial to develop a new treatment, all for very personal reasons.

While treatments for some childhood cancers have developed significantly over the last few decades, there has been little progress for children with diffuse midline glioma (DMG), until recently known as diffuse intrinsic pontine glioma (DIPG).

DMG develops in parts of the brain that control bodily function. The tumour cells become mixed with normal brain cells, rather than a defined tumour, which means removing the cancer via surgery is impossible. While radiation therapy can sometimes temporarily halt the tumour growth, it usually grows back, often more aggressively.

Amanda Mifsud, founder and trustee, Abbie’s Army

Abbie’s Army is a parent-led children’s brain tumour research charity with a specific mission. Founded in 2012, it is driven by the painful loss of our daughter Abbie (pictured), and the clear need for research funding and awareness for DIPG/DMG.

Abbie was just six years old, and her disease was so aggressive that she survived for only five months after her DIPG diagnosis.

With a decade of involvement in the DIPG/DMG research field and parent community, we are acutely aware of the impact of this disease. If you are among those families essentially receiving a ‘death sentence’ for their child, then you fully understand it is the most emotionally challenging thing a parent can ever face. We focus only on overturning this horrendous prognosis.

For many families, clinical trials are the only glimmer of hope, but any new opportunities must be of the highest quality and standard. So, when the possibility arose to collaborate with GOSH Charity to support the provision of the first use of CAR T-cell therapy for DMG, we were compelled to help make this a reality.

Led by Dr Karin Straathof, Associate Professor at the University College London Cancer Institute and Honorary Consultant at Great Ormond Street Hospital (GOSH), in collaboration with Professor Darren Hargrave, a Great Ormond Street Hospital Children’s Charity (GOSH Charity) Clinical Professor in Paediatric NeuroOncology, the trial will involve using a patient’s own immune system to attack the cancer cells. Known as CAR T-cell therapy, this involves modifying immune cells, called T-cells, to hunt down and kill cancer cells.

Pioneer speaks with the charities who are making it possible.

We can only hope that we see some of the same success researchers have gained in childhood leukaemia in recent years, and that this powerful immunotherapy finally tackles these particularly difficult to treat tumours.

Our greatest wish is that we begin to extend life for these children, beyond the direst statistics known for any childhood cancer type. In time, we hope this groundbreaking research builds the foundations needed for CAR T-cell therapy to become a kinder standard of care for children with brain cancer in the UK.

Lola Manterola, founder and trustee, CRIS Cancer Foundation

Since its foundation almost 12 years ago, CRIS Cancer has supported the fight against DMG in different research centres across Europe. We are delighted to be part of this clinical trial in association with GOSH, which we know to be instrumental in pioneering new cancer treatments. CRIS Cancer has also funded trials in immunotherapy since we started, and we have seen some incredible results. These are exciting and hopeful times.

We want to change the cruel diagnoses that are given to patients and their families. We expect immunotherapy to open up new pathways of hope, and success in treatment, so that babies, children and their families do not have to go through such pain and heartbreak when diagnosed with DMG. We are determined to see better rates of survival in the near future, moving quickly towards 100% of those diagnosed going on to live long and fulfilling lives.

It is through joined up learning, research and collaboration that the best results in finding cures for disease are achieved. This collaboration has been an incredibly smooth process, with the knowledge that we are all committed to eliminating this disease giving us a powerful bond. We would encourage others to do the same – together we will transform the lives of future generations.

Cristian Parrino, CEO, The Azaylia Foundation

The Azaylia Foundation was established by Safiyya Vorajee and Ashley Cain after the death of their eight-month-old daughter Azaylia to acute myeloid leukaemia in April 2021.

Millions of people were inspired by Azaylia’s journey, her beautiful smile, her bravery and her perseverance, raising over £1.5 million to fund treatment in Singapore after options offered by the NHS were exhausted. Unfortunately, Azaylia never made it onto that aeroplane, and the funds raised were instead used to start her legacy.

The Azaylia Foundation works closely with leading hospitals and cancer research institutions, donating towards research that can advance early diagnosis and accelerate the availability of new treatments in the UK. We want to enable a future in which no parent is forced to rely on expensive treatments abroad to save the life of their child. This trial is a perfect example, it is bringing an innovative and crucial treatment to the UK, in an area of cancer with extremely low survival rates, and in which parents’ last option and hope is to seek expensive treatment abroad.

Bryn Williams, founder, Funding Neuro

I was diagnosed with Parkinson’s Disease in my mid30s in 2007 and set up Funding Neuro in 2011. Rather than focus on one neurological condition, such as Parkinson’s, Funding Neuro looks to find common problems that affect many conditions and aims to pioneer treatments, accelerate cures and thus save lives! Chief among the common problems in neurological conditions is finding a way to get drugs into the brain through what’s known as the blood-brain barrier.

Funding Neuro had for some time been working to deliver a UK-based DIPG trial and had facilitated compassionate treatment for a number of children from across the UK and Europe. While these treatments extended lives and resulted in a well-received scientific paper, a number of issues resulted in the trial being delayed. Yet with the foundations laid for this trial, we remain hopeful that it will be delivered in due course.

With around 40 children diagnosed with DIPG each year in the UK, we were determined to get a trial running as quickly as possible to deliver some hope to those families who have to endure this disease with no effective treatment.

We hope the trial provides a breakthrough for DMG survival rates worldwide, and that it leads to treatment becoming available via the NHS for children diagnosed with DMG.

GOSH is home to innovators in the research and discovery of new treatments for childhood cancer, and it has been an absolute pleasure to work with them and support this clinical trial.

Having met Professor Darren Hargrave, we were delighted to assist him and Dr Straathof in this trial, as it offers hope of an effective treatment and eventual cure. To assist GOSH Charity to deliver this trial was in many ways a ‘no brainer' and we hope to work with the charity and other funders in many more DIPG trials until a cure is found.

Simone and Nadim Nsouli, founders, The Lyla Nsouli Foundation for Children’s Brain Cancer Research

Our foundation was established in memory of our daughter Lyla, who was diagnosed with DIPG on 13 August 2011 at the age of two years and eight months. The foundation’s aim is to improve the prognosis and eventually find a cure for the worst forms of brain cancer by funding medical research.

Children’s cancer research is consistently underfunded, and rare cancers like DIPG (the deadliest paediatric brain cancer) are the most neglected. We need research that is dedicated specifically to understanding and treating DIPG and rare children’s cancers, rather than continuing to apply adult cancer treatment strategies without success.

We decided to support this trial because of its specific focus on DIPG and because it explores a novel therapeutic approach to treating this rare and cruel disease. Dr Karin Straathof and her team, including Professor Darren Hargrave, who was Lyla’s doctor, have demonstrated their commitment, steady progress and success in this area of research, with promising findings in the preclinical lead up to this trial.

We hope the trial achieves results that begin to demonstrate an effectiveness of CAR T-cell therapy for targeting DIPG tumour cells without any significant downside to children. If this study can ultimately lead

to an effective treatment methodology for destroying DIPG tumour tissue, it would be transformative and unprecedented for DIPG patients.

We know first-hand the importance and value of having GOSH in the UK. Paediatric illness requires unique care, skills and expertise and it is only with adequate funding that institutions like GOSH can continue to offer the best medical care and support transformative research to save children’s lives.

SOLVING A MEDICAL MYSTERY

When public health officials detected an increase in hepatitis cases in children in early 2022, they turned to an expert genomics team at GOSH to investigate why.

Hepatitis, which is used to describe inflammation of the liver, is usually caused by a viral infection. In children, symptoms of hepatitis can include abdominal pain, nausea, yellowing of the skin and eyes (jaundice) and a high temperature. While some types of hepatitis can pass without any serious problems, others can cause more lasting damage.

Doctors in Scotland first noticed an unusual rise in hepatitis cases in young children in April this year. By July, the World Health Organisation (WHO) reported more than 1,000 children across 35 countries had been affected. This included 270 confirmed cases in children aged 10 and under in the UK as of 19 July. Of these children, 15 have required a liver transplant due to rapid liver deterioration.

However, none of the usual hepatitis causing viruses appeared to have caused the liver disease seen in these children.

To identify which virus may be driving the increasing case numbers, the UK Health Security Agency (UKHSA) called on world-leading genomics experts from the Great Ormond Street Hospital (GOSH) Department of Microbiology and the University College London (UCL) Genomics Pathogen Sequencing Group, based in GOSH and the Zayed Centre for Research into Rare Disease in Children.

The team is among just a handful of laboratories in the world that can provide highly specialised metagenomics services.

”We run a diagnostic metagenomic service and we carry out lots of tests from all over the world –we’re getting to be quite well known,” says Professor Judith Breuer, Clinical Professor of Virology at UCL Great Ormond Street Institute of Child Health and Honorary Consultant Virologist at GOSH.

“The UKHSA had this hepatitis of unknown origin, and they wanted to see whether there were any unknown pathogens causing it, so they sent samples to us for testing.”

METAGENOMICS SEQUENCING

Thanks in part to early funding from Great Ormond Street Hospital Children’s Charity (GOSH Charity), GOSH Microbiology, together with UCL, established the Reuben Centre for Paediatric Virology and Metagenomics in 2019 to support the diagnosis of severe infection in children. They now process more than 100 samples a year from children and adults around the world and provide routine adenovirus sequencing to help identify transmission of infections and drug resistance.

During this investigation, the team studied 28 cases, including liver samples from five children who required a transplant and blood samples from the remaining children who did not.

It’s very satisfying to find something unexpected that wouldn’t have been found through routine testing.

Dr Julianne Brown

Professor Judith Breuer

Unlike a PCR test, which returns either a positive or negative result for a specific virus, metagenomic sequencing looks for any infectious organism present in a sample.

“Normally when you’re searching for viruses in a diagnostic lab, you have to think of which virus to look for and do a PCR test for it,” says Dr Julianne Brown, a clinical scientist in the GOSH Microbiology team.

“Whereas metagenomics is completely untargeted and has a really broad range. That’s where the utility is – when there’s a strong clinical suspicion of infection but all the routine tests are negative.”

REVEALING RESULTS

It was initially thought that a spike in adenoviruses –common viruses that usually cause mild cold and flu or gastroenteritis symptoms – could provide an explanation for the increase in hepatitis cases.

“There’s a group of viruses that are typically known to cause hepatitis and they were all negative, but researchers did find an adenovirus,” Julianne says. “So we did adenovirus sequencing to see what type of adenovirus it was, as well as metagenomics to see if there were any other viruses or bacteria there.”

What they found was that the common adenoassociated virus 2 (AAV2) was present at high levels in children with unexplained hepatitis. The virus often accompanies infection with adenoviruses and is not known to normally cause disease.

The GOSH researchers, along with colleagues in Scotland, who conducted their own study at the same time, now believe that coinfection with two viruses – AAV2 and an adenovirus, or less often a herpes virus – may offer the best explanation for the onset of severe liver disease in affected children.

CHARITY FUNDING CRUCIAL

Judith says the team’s contribution to investigating the hepatitis outbreak is “just the tip of the iceberg” when it comes to the potential for metagenomics at GOSH.

“It has been an amazing experience to see it used in this way,” she says. “It’s very satisfying to be able to offer the service, and then to find something unexpected [the AAV2] that wouldn’t have been found through routine testing.”

None of the world-leading work would have been possible without funding from GOSH Charity, which helped the team take a research tool out into the real world.

“The charity funding was absolutely critical,” Julianne says. “What often happens is tools are used in research and shown to be very useful, but then never translate into routine clinical use. In this case, we were able to take what was previously a research tool and make it fit-for-purpose for clinical use, which we couldn’t have done without the charity.”

Genomics autosampler at work in the Zayed Centre for Research into Rare Disease in Children.

PARENT’S PERSPECTIVE

When Lily was only nine months old, we noticed that she was losing weight. She was a very happy child and although it didn’t look like anything was wrong, we knew something wasn’t right. We took her to the doctors, but they didn’t have any concerns and we thought it might be a normal part of weaning.

One night we were putting Lily to bed and her eyes started shaking. It was clear she couldn’t see us, and we became really worried. We took her to our local hospital, and we saw a paediatrician who was very concerned and ordered lots of tests. After a week in hospital, Lily had an MRI scan. The doctors told us the scan revealed that Lily had a brain tumour. It was so shocking; you don’t ever think you will hear those words.

GOING TO GOSH

Lily was referred to Great Ormond Street Hospital (GOSH) and put on steroids straight away to reduce the swelling that had built up because of the tumour. The team at GOSH told us Lily had a type of brain

tumour called a benign optic pathway glioma. She was also diagnosed with visual impairment and a rare condition called diencephalic syndrome. This syndrome is caused by the tumour and can cause euphoria, which explained why Lily had appeared outwardly happy for months despite everything.

Lily moved to Elephant Ward to start chemotherapy, but the journey wasn’t straightforward. After a year of treatment, she had an anaphylactic reaction to one of the chemotherapies and ended up having a shunt fitted. After two years of treatment, the tumour started growing again. We went through a two-week process of preparing for major surgery, but the day before the operation, another scan showed that the tumour had reversed its growth and shrunk quite dramatically.

At the beginning of 2021 things were looking up – Lily’s hair had started to grow back, and we were feeling positive. But in March we found out her tumour had continued to grow, and Lily began another round of chemotherapy which made her so unwell she couldn’t walk.

Lily-May (Lily) came to GOSH when she was a year old after being diagnosed with a brain tumour. Lily’s Mum and dad, Lianna and Stephen, tell Pioneer their story.

Lily has endured chemotherapy for four years, so we’ve had to build our lives around her treatment. We haven’t had a normal Christmas since 2017 – even before the pandemic we’d spend the festive period wearing masks. The staff at GOSH are brilliant, they are dedicated to you and your child. Lily has missed so much school, so the playrooms have been a fundamental part of our stay. The Play team are great, and even when the playrooms were closed due to the pandemic, Jennie from Safari Ward went above and beyond to bring toys to keep Lily entertained.

RINGING THE BELL

Lily rang the end of treatment bell in February. She has technically finished treatment three times already, so for us the day was a real a mix of emotions. We were very anxious, wondering if it would truly be the end of treatment this time, but we still wanted to make sure it was a really special day for Lily. The hospital set up the bell in Queen Square and it was brilliant. Lots of family and friends joined us, and we threw confetti and went out for pizza! It was just the perfect day for Lily.

LILY-MAY TODAY

Lily is five now, but she has been forced to grow up quickly. She is very independent, talkative and insightful. She loves being on camera, baking and doing hair and makeup tutorials. She knows she has a brain tumour; she calls it a ‘puddle’ in her brain, and she blames it if she forgets something or is taking ages to get ready, which makes us laugh.

We still go to GOSH about twice a month, but we really hope that she can move on and form her own life outside of her treatment and condition.

FUNDRAISING FOR GOSH CHARITY

Through our TeamGOSH fund, we have raised nearly £50,000 for Great Ormond Street Hospital Children’s Charity (GOSH Charity), including £10,000 for the Sight and Sound Centre. Lily’s eyesight has gradually deteriorated in one eye over time, so she now visits the Sight and Sound Centre for her eye tests. The old facilities were very outdated – visiting feels so much calmer now. We’ve got a real appreciation for the little things that went into making the building, it feels incredibly special to have been a part of it.

Fundraising is our family’s way of channelling our experiences and feelings over the past five years into something positive. We’ve organised big fundraising events with ticket entry and a raffle, which spiralled into an auction, and Stephen’s work colleagues completed the Three Peaks challenge. GOSH Charity has done a lot for us, and we want people to know this. The hospital thrives from its donations and it’s hugely important to us that we keep doing everything possible to keep the hospital improving.

Great Ormond Street Hospital Children’s Charity 40 Bernard Street London WC1N 1LE 020 3841 3131 gosh.org

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

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