Research Training Fellowship*: Dr Karin Tuschl
First published on 14 May 2012
Updated on 2 July 2018
What did the project achieve?
“Our results have improved our understanding of how manganese is handled by the body, leading us towards an existing drug with exciting potential as a new treatment for children with manganese toxicity,” says Dr Karin Tuschl of Great Ormond Street UCL Institute of Child Health.
Manganese is a trace element that is essential for good health. But if levels become too high, toxicity can occur – causing debilitating symptoms that include problems with movement.
Those most at risk include children who are born with faults in genes involved with processing manganese in the body. Dr Tuschl has previously identified one such causative gene and discovered another in this study.
“Identifying these two genes will help doctors correctly diagnose affected children and enable improved genetic counselling for their parents about future pregnancies,” says Dr Tuschl.
Dr Tuschl’s team studied the function of the two genes in a series of laboratory experiments, leading them to identify a drug that is already used to treat other conditions, which may also be helpful in children with manganese toxicity.
“We showed this drug can lower blood manganese levels in patients,” says Dr Tuschl. “Strikingly, treatment of one child who was severely affected led to such a dramatic improvement of her symptoms that she even regained her ability to walk.”
Evidence is also mounting that metal imbalance plays a crucial role in the development of other conditions, including neurodegenerative disorders like Parkinson’s disease.
“Our findings are not only important for children affected by rare inherited conditions, they may also have much broader implications for the treatment of more common diseases,” says Dr Tuschl.
This research was completed on 1 March 2017
Manganese toxicity: tackling this disabling metabolic imbalance
The metal manganese, though essential to health, causes brain damage if levels in the body rise too high. Those who are vulnerable include premature babies fed intravenously and children with a rare metabolic disorder. Manganese has also been implicated in the development of attention deficit hyperactivity disorder (ADHD). Dr Karin Tuschl, of University College London’s Institute of Child Health, is investigating the role of manganese and looking for ways to protect children from its damaging effects.
What is the problem and who does it affect?
Excessive accumulation of manganese – a metal that is normally present in the body in trace amounts – has been linked to several health problems.
‘Manganese toxicity can occur in newborn babies who are being fed intravenously,’ explains Dr Tuschl. ‘Almost every baby who is born very prematurely, before 28 weeks of pregnancy, has to be fed in this way. Manganese toxicity can also occur in children with liver disease and can contribute to Parkinson’s disease in children. Recently, it has been suggested that high levels of manganese in soya-based infant feeds might be implicated in the development of attention deficit hyperactivity disorder (ADHD).’
In 2011, Dr Tuschl discovered that a rare genetic disorder is linked to errors in manganese metabolism.1 ‘Children with this rare disorder typically experience difficulties walking and have problems with fine motor movements, such as writing,’ says Dr Tuschl. ‘Many become wheelchair users in their teens and, sadly, several have died early due to liver cirrhosis.’
Current treatment for this rare illness is inadequate. ‘Children have to attend hospital for around one week every month to have intravenous infusions that take five to seven days,’ explains Dr Tuschl. ‘While children’s symptoms often improve, there is no cure.’
What is the project trying to achieve?
‘I aim to boost understanding of the role of manganese within the body and help to explain how high levels of this substance lead to health problems,’ explains Dr Tuschl. She is developing a new laboratory model of manganese toxicity specifically for this work.
‘I am also looking for better treatments for children who have abnormally high levels of manganese in their bodies, by testing the potential of several different drugs in the laboratory model,’ continues Dr Tuschl. ‘My ultimate aim is to find a treatment that alleviates physical disability – so children don’t lose their ability to walk, for example – protects the brain and spares children from losing their lives to liver damage.’
Dr Tuschl also aims to offer genetic testing to any children who are suspected of having the rare genetic disorder that is linked to errors in manganese metabolism, so that they can get an accurate diagnosis.
What are the researchers’ credentials?
Dr Tuschl is a talented young doctor who is being guided by world-leading supervisors and mentors. ‘I feel very privileged to have the opportunity to work on this exciting project,’ says Dr Tuschl. ‘It has real potential to help to improve quality of life for children and their families.’
|Project Leader||Dr Karin Tuschl MD MPhil|
|Location||Clinical and Molecular Genetics Unit, University College London Institute of Child Health|
|Grant awarded||14 February 2012|
|Start date||3 September 2012|
|End date||1 March 2017|
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- Tuschl K et al. Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man. Am J Hum Genet 2012; 90:457-66.
*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.