Targeting rare diseases in children

Brittle bone disease: potential of stem cell therapy

First published on 21 January 2014

Updated on 20 January 2014

What did the project achieve?

Researchers led by Dr Pascale Guillot, now at University College London, are developing a new treatment for brittle bone disease.

Babies with this disease are born with fragile bones that break easily. For some, everyday activities such as changing nappies – or even just a simple cuddle – can lead to fractures. They can experience other problems too, such as hearing loss, skeletal deformities and restricted growth. Around one baby in every 15-20,000 is affected.1

“Brittle bone disease can be diagnosed during pregnancy,” explains Dr Guillot. “We believe it may be possible to treat babies while they are still in the womb using special cells called stem cells. We have shown, using a laboratory model of the disease, that transplanting stem cells during pregnancy reduces the occurrence of fractures after birth and improves bone strength.”

“The stem cells we’ve been using were taken from the placentas of healthy human babies,” continues Dr Guillot. “They can easily be obtained during routine pregnancy check-ups or after birth. More research is needed before we can start testing treatment in babies, but we believe it may one day mean children with brittle bone disease have stronger bones, develop fewer physical deformities and suffer fewer fractures.”

This research was completed on 7 March 2013

Children with brittle bone disease have such fragile bones they can suffer fracture after fracture, often with little or no apparent cause. The disease can cause other problems too, such as hearing loss and retarded growth. Sadly, the most severely affected babies die soon after birth. There is no cure, but a recent breakthrough suggests stem cells could have the potential to boost bone strength and cut fracture rates. Researchers are exploring this in the laboratory.

What's the problem and who does it affect?

Fragile bones

Babies with brittle bone disease – also known as osteogenesis imperfecta – are born with fragile bones that break easily. Some suffer broken bones while still in the womb.

The severity of the disease varies greatly. Children with mild disease may suffer only a few fractures, whereas others can have hundreds over their lifetime. Everyday activities, such as changing nappies, bathing and dressing the child, or even just a simple cuddle, can lead to fractures.

Brittle bone disease can cause many other serious problems. Some children, for example, develop a curved spine or bowed legs, their growth may be retarded, and they may suffer muscle weakness, fatigue, hearing loss, brittle teeth and constant pain in their bones. Vital organs can also be affected, including the lungs, heart and kidneys. Sadly, the most severely affected babies die soon after birth.

An estimated 4,000 people in the UK have brittle bone disease.1 Treatments include occupational therapy, physiotherapy, wearing casts or braces to support broken or weakened bones, taking drugs called bisphosphonates, and surgery to insert metal rods into bone shafts. There is, however, no cure, and many children continue to suffer fractures despite treatment.

What is the project trying to achieve?

Breakthrough discovery

Brittle bone disease is a genetic disorder, which is sometimes inherited and sometimes arises by chance. Symptoms result from a defect in a protein called collagen, which has a major structural role in bones, joints, teeth and skin.

A recent breakthrough suggests that transplanting stem cells from healthy babies, who have normal collagen, to babies with brittle bone disease could be beneficial: work in a laboratory model of the disease showed that transplanting stem cells during pregnancy reduced the number of fractures in some bones by 75%; bones also became stronger and thicker.

However, the stem cells used in this research came from the bloodstream of unborn babies. These cells cannot be taken routinely, for safety and ethical reasons.

Another, more accessible source of stem cells is the placenta. So, in this project, the researchers are taking stem cells from human placentas - both during pregnancy and at birth – and exploring the therapeutic benefits of these cells in the laboratory model. They are also studying how the timing of transplants affects results.

What are the researchers' credentials?

Project LeaderDr P V Guillot CASLAT
Project team
  • Dr Paolo De Coppi PhD MD
  • Professor Dame Julia Polak DSc, FRCPath, MRCP, FRCP, FMedSci, ILT
LocationInstitute of Reproduction and Developmental Biology (IRDB), Hammersmith Hospital in conjunction with Surgery Unit, UCL Institute of Child Health, Great Ormond Street Hospital and Department of Chemical Engineering, Imperial College London.
Other locations
  • Institute of Child Health and Great Ormond Street Hospital
  • Department of Chemical Engineering, Tissue Engineering and Regenerative Medicine, Imperial College, London
Duration3 years
Grant awarded23 July 2009
Start date8 March 2010
End date7 March 2013
Grant amount£180,346.00
Grant codeSP4431, GN1749

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The researchers are world experts in the therapeutic use of human stem cells isolated from babies during pregnancy. They made the groundbreaking discovery that stem cells from a healthy baby’s bloodstream can reduce fracture frequency by two thirds in a laboratory model of brittle bone disease.

The researchers regularly isolate stem cells from other, more accessible, fetal sources, such as the placenta and the amniotic fluid (the waters that surround babies in the womb). They recently showed that stem cells isolated from babies during pregnancy have some advantageous characteristics that make them better suited to therapeutic use than stem cells isolated later on in life, such as those from adult bone marrow.

The research will take place at Imperial College, London, which provides an excellent overall environment for such work.

Who stands to benefit from this research and how?

An important step towards a new treatment

The breakthrough discovery that stem cell transplants can decrease fracture rates in a laboratory model of brittle bone disease suggests similar transplants may one day benefit babies with the illness. In this project, the researchers hope to provide proof of principle that the placentas of healthy babies could provide a suitable source of stem cells for such transplants.

Researchers envisage unborn babies could be given stem cell transplants during pregnancy, when the cells would be infused into a baby’s bloodstream. As stem cells can be stored for future use, it would be possible to give further transplants after birth, during childhood and in adult life.

The researchers believe early treatment during pregnancy could mean that babies’ bones develop more normally – laboratory evidence suggests bones could be stronger and fracture less easily. In theory, treatment may also prevent irreversible damage to vital organs, such as the lungs.

The ultimate hope is that babies who are diagnosed with brittle bone disease during pregnancy could benefit (it is possible to diagnose the disease in unborn babies during routine prenatal tests).

References

  1. Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet. 2004; 363(9418): 1377-85.