Research Training Fellowship: Dr Manju Kurian
Hunting for genes for two devastating diseases of childhood
Research Training Fellowships
Each year, Action Medical Research awards these prestigious grants to help the brightest and best doctors and scientists develop their career in medical research. Dr Kurian’s grant of £135,648 will fund her two-year study into two devastating genetic disorders that cause death and disability in children.
Dr Manju Kurian
After completing medical school at Cambridge University, Dr Manju Kurian specialised in paediatric neurology – caring for children with diseases of the nervous system. She was dismayed to find that some children suffer a range of severe and disabling symptoms, such as seizures, spasticity, blindness and learning difficulties, with limited relief from modern medicine. A dire lack of understanding of what causes these problems badly hinders their treatment.
In this Fellowship, Dr Kurian is unravelling the molecular causes of two particularly devastating diseases. Her intelligence, enthusiasm and diligence stand her in good stead for achieving these important goals.
‘Dr Manju Kurian: ‘I am absolutely thrilled to receive this training fellowship from Action Medical Research. I feel very privileged to be part of such exciting research, which could impact so greatly on children’s lives.’
Dr Manju Kurian
The problem
Heartbreaking suffering in children
Dr Manju Kurian is investigating the genetic basis of two inherited disorders of the nervous system: infantile spasms and MRST syndrome.
Estimates suggest around 175-300 babies and children develop infantile spasms each year in the UK.1,2 Typically, they develop normally until they are around 4-7 months old, when they suffer their first seizure.
‘Children with infantile spasms have multiple seizure clusters on a daily basis,’ explains Dr Kurian. ‘Over time, some children can regress – almost completely losing previously acquired skills. They can develop severe learning disabilities, as well as abnormal muscle contractions that compromise their mobility. Their anti-epileptic medication causes side effects, such as high blood pressure, infection, irritability and deteriorating eyesight, and many are regularly admitted to hospital, with uncontrollable seizures and recurrent chest infections.’ Sadly, some children lose their lives to their illness. Many gain limited benefit from existing treatments.
The second disease that’s being investigated, MRST (which stands for mental retardation, spasticity, tapetoretinal degeneration), is less common but just as devastating. Affected children have learning difficulties, physical disabilities, due to the stiffness in their arms and legs, and they eventually lose so much of their sight that they become blind.
Dr Kurian's research
Hunting for genes
Little is known about the underlying causes of infantile spasms and MRST, making it difficult to develop new treatments. Dr Kurian hopes to fill this dire information gap. ‘My research aims to understand the molecular processes that lead to infantile spasms and MRST, by identifying the genes that cause them, and then investigating the function of the genes.’
Several large, extended families have agreed to take part in the research. They all include children who are suffering from infantile spasms or MRST. Both affected and unaffected family members are providing samples of their DNA.
‘I can’t thank Action Medical Research enough for this wonderful opportunity to work towards improving the lives of children with these devastating diseases,’ says Dr Kurian.
Who stands to benefit from Dr Kurian's research and how?
Genetic counselling, earlier diagnosis and new treatments
Identifying the genes for infantile spasms and MRST could lead to many benefits in the future, as Dr Kurian explains. ‘Identifying the genes would allow us to diagnose the conditions earlier, and help us predict how a child’s illness is likely to progress. We would be able to give more accurate genetic counselling to families with affected children, by assessing each couple’s chance of having children with the same condition in the future, and offering prenatal testing during pregnancy. A greater understanding of the disease process would also help in the development of new treatments, which are desperately needed.’
Dr Kurian’s research will be of direct benefit to families affected by infantile spasms and MRST, but it may eventually lead to even wider benefits. Epilepsy, mental retardation and spasticity are all major causes of disability worldwide, and boosting our understanding of the disease processes involved could help other people with these problems.
For Dr Kurian, this Fellowship brings personal benefits too. ‘I feel extremely privileged to be in this very fortunate situation where my research is funded,’ she says. ‘I feel that working in this area of research is a true vocation for me.’
More details on Dr Kurian’s research project
The two diseases that Dr Kurian is studying are both inherited in an autosomal recessive way, which means a person can be an unwitting carrier of the gene without actually having the illness themselves. Children are affected when both their parents are carriers, and they inherit two copies of the disease-causing gene – one from each parent.
Dr Kurian’s work is focused on identifying genes which cause infantile spasms and MRST. DNA from a single large consanguineous family – an extended family in which some of the cousins have had children together – could provide enough information to identify the gene, and several such families have volunteered to take part in this study.
Dr Kurian visited one mother, for example, who had already lost two children to epilepsy. She was caring for a third child, whose similar debilitating illness was not responding to treatment. ‘I was overwhelmed by the mother’s enthusiasm for life and her living child, as well as her support for the research. She and her family are really an inspiration to work hard and find disease-causing genes in this devastating condition. I feel very passionate about the need for this research.’
Throughout her Fellowship, Dr Kurian will receive top-class training in highly sophisticated laboratory techniques. ‘My supervisor’s laboratory (the Maher group) is world-renowned in the field of autozygosity mapping – the technique that I am using to find the disease-causing genes,’ she says.
References
1. Cowan LD, Hudson LS. The epidemiology and natural history of infantile spasms. J Child Neurol 1991; Oct 6(4): 355-64.
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2. Office of National Statistics. Health Statistics Quarterly 35 (Autumn 2007) Table 2.1
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