Cambridge scientists to pioneer new technique to diagnose medulloblastoma

When little Sophie Harper started vomiting regularly, a doctor believed it was a virus.

But months later, she started to lose her ability to walk – and a hospital scan revealed a type of brain tumour known as medulloblastoma.

A seven-and-a-half hour operation followed, and it had major side effects.

Now, with funding from The Brain Tumour Charity, Cambridge researchers are pioneering novel, minimally invasive techniques for the diagnosis of medulloblastoma, which could help some children avoid such surgery.

Medulloblastoma is the most common cancerous childhood brain tumour, accounting for 15-20 per cent of all such diagnoses. About 52 children are diagnosed with a medulloblastoma each year in the UK.

These fast-growing tumours develop at the back of the brain in the cerebellum, and there are four sub-types.

Dr Jessica Taylor, a postdoctoral researcher at the University of Cambridge working in Professor Richard Gilbertson’s lab at the Cancer Research UK Cambridge Institute, will focus on one of them – wingless (WNT) medulloblastoma.

This is typically difficult to operate on, but is highly curable with chemotherapy and radiation.

A Future Leaders award from The Brain Tumour Charity will enable Dr Taylor to explore a new method of identifying WNT medulloblastoma without invasive surgery to protect children from the potential long-term damaging effects it can have, such as memory problems and speech issues.

Antibodies designed to bind to the WNT-medulloblastoma cells will be used, so that they are visible on a PET scan to help diagnose the condition.

Dr Taylor is using a method of mapping the surface proteins on tumour cells to design these labelled antibodies that bind to cancer-specific receptors but avoid healthy ones.

The researchers will also design these antibodies to bind to drugs that could treat WNT-medulloblastoma, which could deliver treatments directly to the tumour and potentially replace the need for more traditional chemotherapy.

That would give patients an additional treatment option and offer a more targeted therapy, potentially reducing side effects.

John Huggins, the grandfather of Sophie Harper, knows how valuable that could be.

Sophie was diagnosed with medulloblastoma in 2006.

John said: “Until the age of 19 months, Sophie seemed to be a normally developing little girl. She walked at 11 months and her speech was well ahead of her age. From 19 months she started to vomit regularly and when her mother took her to the doctors on day four, he diagnosed a virus. After 10 days my daughter returned to the doctor, but again he said it was a virus. Sophie was taken to the doctor a number of times over the next two and a half months and there was no change with the doctor’s diagnosis.

“Sophie then started to lose her ability to walk. No longer was she the happy child, she was complaining of head pain, started falling over regularly and wanting to be carried around. It was only then the doctor agreed for Sophie to have a scan.”

A scan at Norwich University Hospital revealed a mass on her cerebellum and Sophie was transferred for further tests to Addenbrooke’s Hospital in Cambridge, where a medulloblastoma tumour was confirmed.

John said: “None of us had any knowledge of brain tumours and it became a huge learning curve. At that point mum and dad had to decide whether to take the option of curative or palliative care. Sophie always had a big personality and was such a fighter with any illness, so mum and dad decided they had to give her the tools to fight with and take the curative option.”

The next week, the operation took place and the family waited anxiously in the garden of Addenbrooke’s. The operation was expected to last around three to four hours, but Sophie was in surgery for seven and a half.

John said: “Sophie didn’t regain consciousness for 32 days, due to the insult to her brain. She spent three months in intensive care and was now needing an oxygen supplement and having to be fed through a gastrostomy tube. Both of these would stay for the next six years of her life.

“It also became clear that there were other side effects from the operation: her speech was significantly impacted and she was unable to hold our gaze and her movements were unco-ordinated and clumsy. During the time of her treatment she received more than a hundred transfusions of blood products due to low blood cell counts, but none of us can remember a single day when she didn’t make us laugh or brighten our day. She had an amazing ability to do that.

“It is true to say surgery had a dramatic effect on Sophie. She was no longer the child we knew before the operation.”

Devastating news came just before Sophie’s eighth birthday, when a scan revealed another growth on her brain.

She was given three months to live, but survived almost a year and died shortly before her ninth birthday in 2013.

Sophie’s family then set up The Sophie Elin Harper Fund with The Brain Tumour Charity to raise funds and awareness of brain tumours. So far, they have raised a remarkable £38,000.

John said: “The side effects Sophie had following surgery, with the insult to her brain, were huge and totally life-changing.

“Sophie lived a very cruel life, in and out of hospital. Even the shunt fitted in her brain had to be replaced on three occasions. She never regained the ability to walk, and was always fed through a gastrostomy tube, together with an oxygen supplement, but she never complained.

“The possibility of avoiding side effects and unnecessary surgery would be a real turning point in the treatment of medulloblastoma.”

Dr Taylor said: “Over 50 children in the UK are diagnosed with medulloblastoma every year and ensuring that these children get the best treatment is of paramount importance to ensure they have a good quality of life.

“We know that WNT- medulloblastoma is difficult to resect surgically, but responds well to standard of care treatment. We hope that our research can avoid unnecessary surgeries in the future.

“With one in four children with this tumour type suffering long-term memory loss and speech issues after surgery, it is important that we work towards improving diagnostic methods which avoid surgery.

“I hope my research will change the way medulloblastoma is clinically diagnosed and that it will improve the treatment and quality of life for children diagnosed with this disease.”

Dr David Jenkinson, chief scientific officer at The Brain Tumour Charity, said: “Our Future Leaders are the next generation of brain tumour researchers. Their innovative ideas and determination to find a cure will drive us closer to improving the lives of those diagnosed with a brain tumour.”