Europe-wide project launched that uses stem cells to treat brittle bone disease in the womb

A trial that uses stem cell injections to treat osteogenesis imperfecta, more commonly known as brittle bone disease, prior to and just after birth has been launched by teams at Great Ormond Street Hospital (GOSH) and the UCL Institute of Child Health (ICH) in collaboration with colleagues across Europe.

By carrying out genetic screening in pregnant women whose baby is suspected of having severe osteogenesis imperfecta (OI), babies identified with the condition may be treated with a stem cell that increases the production of collagen in the body. This then reduces the number of painful bone fractures a child experiences once born.

OI affects around one in 15 – 25,000 people in the UK and is characterised by painful fractures in bones throughout the body. The condition can also lead to a range of other medical problems, such as discoloured ‘brittle’ teeth and hearing impairment as a young adult. In the majority of affected individuals, OI is caused by a defect in a gene that produces collagen – a helix shaped protein that is integral to the strength of bone and other tissues in the body. There is currently no cure for the condition and treatments focus on alleviating symptoms rather than treating the underlying cause.

A team at the Karolinska Institute in Sweden have developed a special strain of stem cells, which when injected into the body of affected individuals, targets and strengthens the bone by producing collagen. Preliminary studies in mice have shown that this can reduce the number of fractures experienced and the injections have also shown some success in alleviating symptoms in a small number of children in their early teens.

The team are now leading a European project to trial administration of the treatment to babies prior to birth and in the years immediately following. They hope that treatment earlier in life will lead to more effective results throughout childhood.

Professor Lyn Chitty’s team in the genetics laboratory at GOSH is set to carry out prenatal testing in at risk women to identify babies with the condition and will then provide genetic counselling to families once a diagnosis is made. If families elect to take part in the trial, a team at University College London Hospital (UCLH) will administer the stem cell therapy in the womb. After birth the babies will be followed up by the team at GOSH and given injections every six months for two years.

The trials will start in early 2016 and are set to recruit over a period of two years. Success of the project will be assessed by comparing fracture numbers in children who had the treatment early on in life with those with OI who haven’t received injections.

Dr Catherine DeVile, Lead for the Osteogenesis Imperfecta Service at GOSH and who will monitor these children clinically after birth, says “OI is a condition that can be debilitating, causing multiple fractures, bone deformity, pain and impaired mobility if severe.

“While injecting these stem cells during teenage years appears to offer some relief in a small number of patients tested, intervention at an early stage in life may lead to more effective results for patients in the long term.”

Professor Chitty explains “Developments in technology mean that more and more conditions can be diagnosed while a child is still in the womb. If successful, this project may be the one of the first to show that certain conditions can begin to be treated prior to birth, leading to better outcomes for the child.”

Former GOSH patient Adam, 21, was treated at the hospital for OI: “I first came to GOSH when I was seven years old for operations to correct breaks in my bones and to have metal rods put in to increase my bones’ strength. More recently, I visited every three months for three days at a time for a calcium and vitamin D treatment that also helped with bone strength.”

“As an adult looking back, I realise that living with the condition was hardest when I was young as I spent so much time in hospital and missed so much school. If I was offered a treatment like this I would definitely have considered it as I could have avoided all the breaks and stays in hospital and I could have got better grades at school!”

The “Boost Brittle Bones Before Birth” (BOOSTB4) project will start in January 2016 and will be coordinated by Karolinska Institutet. Other participating research centres and companies include Great Ormond Street Hospital, University College London, the University of Leicester, Universitair Medisch Centrum Utrecht, Leiden University Medical Centre, Uniklinik Köln, Lund University, Cell Protect Nordic Pharmaceuticals, Nordic Health Economics, MedSciNet and Euram Ltd. The study will also include patients from other European countries. Funding has been obtained from several sources, including the Swedish Research Council and Horizon 2020, the EU framework programme for research and innovation