Sickle cell disease: striving for better treatment
First published on 30 January 2009
Updated on 3 July 2013
What did the project achieve?
Researchers are taking important steps forwards in the search for a cure for sickle cell disease.
Around one baby in every 1,900 born in the UK has sickle cell disease.1 Treatments can help, but there is no cure. Some babies with the disease go on to experience serious problems throughout their lives, suffering attacks of intense pain known as crises and life-threatening complications such as strokes, severe infections and organ failure.
“The symptoms of sickle cell disease result from changes in a protein called haemoglobin, which carries oxygen around the body in the blood,” explains Dr David Carter. “We have shed light on the natural processes that control the production of haemoglobin.”
“More specifically, we have identified factors that seem to control a gene that provides instructions on how to make a healthy form of haemoglobin',” continues Dr Carter. “This gene usually switches off naturally soon after birth. Finding a safe and effective new way to switch this gene back on again might cure sickle cell disease, a crippling illness that affects millions of people worldwide.2 The need for a cure is high and our research continues.”
This research was completed on 5 April 2011
More than 12,000 people in the UK have sickle cell disease.1 They face a lifetime of agonisingly painful attacks, hospital visits and possible complications, including strokes, blindness and organ failure. Sadly, life expectancy is significantly reduced. Perhaps the most successful drug treatment for sickle cell disease is hydroxyurea,2 but this can cause many unpleasant side effects and is not always effective. Researchers are investigating the potential of a possible new approach to treatment.
What's the problem and who does it affect?
A lifetime of crises
Sickle cell disease is one of the commonest inherited diseases, estimated to affect over 20 million people worldwide.2 Symptoms usually start early – in babies who are just six to nine months old.
Sufferers have attacks of intense pain – known as crises – which typically last for anything from a few hours to several days. They are prone to severe infections, particularly chest infections, and periods of anaemia, which can rapidly become life-threatening. They are also at risk of a variety of complications, including leg ulcers, strokes, blindness and organ failure. During pregnancy, women with sickle cell disease are at increased risk of pre-eclampsia and premature labour, which can both be life-threatening for babies.
The only treatment approved to decrease the frequency and severity of crises is a toxic drug called hydroxyurea, but this is only partially effective in most people and ineffectual in others. What’s more, benefits often come at the cost of unpleasant side effects. Treatment often relies on finding ways to manage the various problems that people experience, for example using pain killers during crises, antibiotics to fight infection and blood transfusions for anaemia, but these measures do little to tackle the underlying cause of the disease.
Sadly, people with sickle cell disease face a lifetime of hospital visits and their life expectancy is reduced. They are not expected to live beyond their forties or fifties, and some die in childhood1 Better treatments are urgently needed.
What is the project trying to achieve?
Switching fetal genes back on
Sickle cell disease results from a mutation in the beta globin gene, which codes for part of haemoglobin – the protein that carries oxygen around the body inside red blood cells. The cells become abnormally rigid and sickle shaped, meaning they can get trapped in small blood vessels. The resultant blockages stop oxygen from getting to tissues, causing the agonising pain experienced during crises and eventually serious organ damage.
There is another form of haemoglobin, normally found in babies when in the womb. This is coded for in part by a gene called gamma globin, which is usually switched off shortly after birth.
Some people have unusually high levels of the gamma globin protein throughout their lives. This seems to relieve the symptoms of sickle cell disease. It’s thought that hydroxyurea works by somehow keeping the gene for gamma globin switched on, though it kills many cells in the process – hence its side effects.
Finding a better way to switch the gamma globin gene on could lead to a new treatment, but no-one knows exactly how this gene is normally controlled. The researchers are investigating this using blood samples from healthy volunteers. They are testing whether a technique called RNAi can switch the gamma globin gene on without affecting other genes or killing other cells in the process.
What are the researchers' credentials?
|Project Leader||Dr D Carter PhD|
|Location||Oxford Brookes University Oxford in conjunction with The Babraham Institute, Cambridge|
|Grant awarded||30 October 2008|
|Start date||6 April 2009|
|End date||5 April 2011|
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Between them, the two expert researchers who are working on this project have over three decades of experience of investigating the molecular factors that control the beta globin gene.
The project leader, Dr David Carter, made an outstanding start to his career. After gaining a first class honours degree in biochemistry, he went on to study for his PhD at Cambridge University and then honed his research skills yet further at Oxford University. He is now Lecturer in Biomedicine at Cranfield University, where he has access to state-of-the-art facilities for his research.
Dr Carter is collaborating with Dr Peter Fraser, a world expert in how the beta globin gene is regulated. Dr Fraser has completed seminal work on this topic and contributed to more than 50 peer-reviewed publications. He has been a Senior Fellow of the UK’s Medical Research Council since 1999 and was recently elected to the membership of the European Molecular Biology Organisation (EMBO).
Who stands to benefit from this research and how?
Aiming for a new treatment
The researchers’ work will give us a deeper understanding of how the gamma globin gene is controlled. The team believes this is essential if we are to develop a rational new therapy for sickle cell disease.
If the RNAi technique can switch the gene for gamma globin back on, the researchers plan more extensive studies, with the ultimate aim of developing RNAi as a new treatment for people with sickle cell disease.
The goal would be to develop a new treatment that reduces the severity and frequency of crises, protects people from complications, such as infections, strokes and blindness, and increases life expectancy, without causing problematic side effects.
Large numbers of people are living in hope of a new treatment. Worldwide, over 200,000 babies are born with sickle cell disease each year.1 It’s possible that everyone with the disease may benefit from this research in the future.
- Howard J Davies SC. Sickle cell disease in North Europe. Scand J Clin Lab Invest 2007; 67:27-38.
- Aliyu ZY, Kato GJ, Taylor J, Babadoko A, Mamman AI, Gordeuk VR, Gladwin MT. Sickle cell disease and pulmonary hypertension in Africa: A global perspective and review of epidemiology, pathophysiology, and management. Am J Hematol 2008; 83:63-70.