Cancer drugs could transform the lives of children with serious disfigurements

Drugs normally used to treat cancer could reduce the disfigurements of thousands of children born with life-threatening blood vessel defects, according to research led by Great Ormond Street Hospital (GOSH) and its academic partner, the UCL Great Ormond Street Institute of Child Health (ICH).

Following DNA testing, scientists have been able to pinpoint the group of genes responsible for causing blood vessel defects in arteriovenous malformation (AVM). For the first time, they have identified drugs which could target the underlying cause of the condition.

In AVM, which affects hundreds of thousands of people across the globe, abnormalities in blood vessels lead to painful facial or other disfigurements, life-threatening bleeding and increased risk of complications like stroke. Until now, effective treatment options have been severely limited, with the only options being embolisation or surgery to try to stop growth, or reduce the swellings. However, these treatments often lead to the blood vessels growing back.

This research has now opened the door for highly personalised medical treatment for children with this debilitating condition.

The ground-breaking study, which involved testing the DNA of over 150 children with blood vessel defects including AVM, discovered that a proportion of patients had faults in the group of genes known to be involved in cancers but not previously known to be responsible for the correct formation of blood vessels in the womb. Four genes were found to be faulty in different patients, all on the so-called RAS/MAPK pathway which controls cell growth. This discovery enabled researchers to identify widely used cancer drugs – MAPK pathway inhibitors, which are normally used to counteract faults in the RAS/MAPK genes in cancer cells – as a new potential treatment for AVM.

When tested in the lab on fish with abnormal blood vessels, the drugs reduced the size of the blood vessel swellings and increased blood flow.

The research, which is led by Dr Veronica Kinsler, Consultant Paediatric Dermatologist at GOSH and Principal Investigator and Wellcome Trust Fellow at ICH, will now be tested in an international clinical trial, planned to start next year.

This study is one of over 1000 research projects being carried out at GOSH as part of their pioneering research programme, which aims to develop treatments and cures for rare and complex childhood conditions.

Dr Veronica Kinsler, said: “This is a very exciting and potentially life-saving discovery.

“Understanding that these birthmarks are caused by faulty genes, and in particular that these can vary from patient to patient, is a huge leap forward in understanding the science behind AVM.

“The most exciting part is that there are already approved drugs available to use as part of clinical trials. We’ve seen some very encouraging results in the lab and are hopeful that clinical trials in children will help those suffering with AVM.”

Professor David Goldblatt, Director of Research and Innovation at GOSH, said: “This important research has helped identify a new pathway for treating this very serious and painful condition.

“It is a great example of how research at GOSH is bringing the discoveries made in the laboratory closer to the seriously ill children who need them most.”

Nikki Lilly, was diagnosed with AVM when she was six years old, after being referred to Veronica Kinsler at GOSH. Since then, the 13-year-old has had more than 330 appointments and undergone dozens of procedures.

Nikki has high flow craniofacial AVM on the right-hand side of her face and, as part of Professor Kinsler’s research, was found to have a fault in the RAS/MAPK genes. Based on the findings of the study, Nikki began taking medication. And in the six months since then, there has been no growth in her AVM. However, it is too early to say whether the treatment has been effective.

Nikki is an extraordinary girl, who has never been held back by her condition. A keen beauty and baking vlogger, she has nearly 300,000 subscribers on YouTube and is a reporter for children’s channel CBBC. Her parents George and Tanya set up the Butterfly AVM Charity to support families affected by the condition. The charity has so far raised more than £250,000 and provided a grant to help fund this research.

Nikki said: “I was excited to take part in the study as I thought being able to take a drug to control or shrink my AVM would be a lot less painful than having regular operations.

“As I have only been on the drug for just over six months it’s not enough time to really tell, but the first scans have been positive and show no further growth. I do feel very tired sometimes and I have a rash on my face and still get some nosebleeds, but none that have required transfusions."