Oxford study funded by Action Medical Research puts devastating, disabling childhood ataxias ‘on the map’

A team of researchers led by Professor Andrea Nemeth at the University of Oxford have discovered several new genes linked to a rare, devastating neurological condition known as childhood onset ataxia.

The £173, 364 study funded by children’s charity Action Medical Research has been a very successful step into understanding genetic causes of childhood ataxias.

And, by bringing about improved awareness and availability of genetic testing, this work is already benefitting children and families affected by this heartbreaking condition.

Consultant in Neurogenetics Professor Nemeth says: “Ataxias are actually a group of different disorders, all characterised by loss of balance and co-ordination. Some ataxias are progressive and in those cases children may slowly lose their ability to walk, and eventually need to use a wheelchair. Their speech can become slurred and everyday tasks – even just reaching out to have a drink of water – can become difficult.”

She adds: “However, not all ataxias are progressive and it is often uncertain what a child’s future holds – that can be so difficult for a family.”

Estimates suggest there are at least 10,000 adults and 500 children with progressive ataxia in the UK¹.

But, even where there is a strong family history, most children do not receive a definite genetic diagnosis. This leaves families uncertain about how best to help their child and anxious about the future.

“Identifying the underlying genetic cause can provide information on the type of ataxia, and specifically whether it is likely to be progressive or not. But genetic testing is only possible for known genes, hence the excitement at identifying new genes associated with this condition,” says Professor Nemeth.

She adds: “New genetic tests for ataxia could also spare children from going through more traumatic tests, such as lumbar punctures and MRI scans.”

With funding from Action Medical Research, Professor Nemeth and her team worked with more than 30 families over two and a half years, decoding genetic information (DNA) and developing cellular models to help understand brain development.

Disease-causing changes in around 60 human genes have already been shown to be linked to ataxia, but Professor Nemeth’s previous research indicated that many children who have inherited the condition do not have changes in these genes. So the team set out to look for disease-causing changes in other genes – and successfully identified four new genetic causes of childhood onset ataxias.

The researchers were able to offer much-needed information, advice and genetic counselling to parents: “It has been possible in some cases to provide reassurance for families where a condition will not deteriorate and in future some cases may be suitable for drug treatment,” Professor Nemeth says. “Our work has also helped parents make decisions about having more children.”

In addition, the study found that that the majority of children with congenital ataxias also have learning difficulties. “This suggests that the gene mutations are having widespread effects, and is an area which merits further investigation,” says Professor Nemeth.

The team also made important discoveries in relation to ataxic cerebral palsy, and their findings have been published in the prestigious journal Brain.

“Cerebral palsy is normally considered to be a condition arising from injury at or just before the time of birth,” Professor Nemeth explains. “Some cases of ataxic cerebral palsy may now be redefined as genetic conditions. This has potentially huge implications both for future research in this area and genetic counselling.”

The researchers plan to continue their work to improve diagnosis, and provide prognostic information and genetic counselling for these families. In the future, new drug treatments may also become possible. Although there is still much work to be done, the team believes this project has successfully put childhood ataxia on the map.

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References

1. Ataxia UK (Management of the ataxias: towards best clinical practice, 3^rd edition, 2016). https://www.guidelines.co.uk/ataxiauk/ataxia

Notes to editors

1. Ataxias are neurological disorders of balance and coordination which can cause significant physical disability. They result from damage or degeneration of nerve cells in and around the part of the brain that controls muscle coordination, known as the cerebellum, or diseases that damage the spinal cord and peripheral nerves. The hands, arms, legs, body, speech and eye movements can be affected.
    
2. Professor Nemeth is a Consultant in Neurogenetics and Associate Professor, Oxford University Hospitals NHS Trust and University of Oxford.
    
3. In 2015 Professor Nemeth was awarded the title of Associate Professor as a result of academic excellence whilst working within the NHS. She has written the Genetics section of the guidelines for health professionals produced by Ataxia UK (Management of the ataxias: towards best clinical practice, 3^rd edition, July 2016) providing information on which genetic tests to conduct and how to access testing.
    
4. International Ataxia Awareness Day is on Sunday, 25 September 2016

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