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Argininosuccinic aciduria: developing a new treatment for this rare disorder

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What did the project achieve?

“This study takes us one step closer towards getting our innovative new gene therapy into a clinical trial,” says Dr Julien Baruteau of the UCL Great Ormond Street Institute of Child Health.

Argininosuccinic aciduria (ASA) is a rare inherited disease that has a devastating impact on children’s lives. Although babies appear healthy when they are born, they can soon develop life-threatening symptoms. If treatment is given early it can be life-saving but it’s intensive, complex and difficult to follow.

Dr Baruteau is working to develop a new gene therapy that corrects the faulty gene in the brain and liver of affected babies. The hope is that this could reduce the severity of their illness, or even provide a cure.

“The results from our initial laboratory tests are so far encouraging, providing a better understanding of the disease and suggesting the most effective potential timings for giving the treatment – one injection just after birth to treat the brain disease and a second in adulthood for treating liver symptoms,” says Dr Baruteau.

Dr Baruteau has also set up a national database of ASA patients and has so far collected information on 55 patients across the UK.

“This valuable resource is helping to improve our understanding of how the disease progresses and also provides a register of patients who might benefit from our new therapy,” he says.

If the approach works, the team is hoping to develop similar treatments for other metabolic diseases, helping more children with these devastating conditions in the future.

This research was completed on

Research Training Fellowship*: Dr Julien Baruteau

Dr Julien Baruteau, of Great Ormond Street Hospital, London, is dedicating his working life to helping children with diseases that affect their metabolism, diseases which can be disabling or life-threatening. There are over 300 diseases like this, which involve changes in chemical reactions within the body.1 Although each individual disease can be rare, estimates suggest that more than one in every 1,000 newborn babies in the UK has one.2 In this project, Dr Baruteau is developing a new treatment for a devastating, inherited disease called argininosuccinic aciduria (ASA).

What is the problem and who does it affect?

“Babies with ASA seem healthy at birth,” explains Dr Baruteau. “Sadly though, within just days they can become very ill. Without early treatment, babies are at serious risk of slipping into a coma and losing their lives. Even with treatment, they can develop life-long problems including learning difficulties, behavioural problems, epilepsy and liver damage.”

Treatment can save babies’ lives, but it is intensive, complex and difficult to follow. Things that place the body under stress, such as infections, can trigger further episodes of ill health, which can be life-threatening.

“Children with ASA must take several medicines and vitamins each day and follow a highly specialised diet,” says Dr Baruteau. “Treatment is so complex that it is very difficult for parents to take a break and entrust their child’s care to someone else. Parents must also be on constant look-out for warning signs that their child’s illness is about to take a turn for the worse, when specialist, emergency care in hospital is often needed.”

Liver transplants can also help, but bring their own risks and there is a shortage of donors. New treatments are badly needed.

What is the project trying to achieve?

“I aim to develop the first-ever gene therapy for ASA,” explains Dr Baruteau.

Gene therapy is a ground-breaking approach to treating inherited diseases such as ASA. All of the symptoms of ASA ultimately result from changes – or mutations – in a single gene. Gene therapy would work by delivering a normal version of that gene to the body.

Dr Baruteau explains: “In theory, giving babies gene therapy just before or after birth could reduce the severity of their illness – or even cure them – and stop them from being so dependent on the intensive treatment that’s needed at the moment. I am in the laboratory stages of my work and hope to start testing gene therapy in children within around five years.”

 “In the longer term, if gene therapy works for ASA, the approach I am using here could be adapted to help children with other metabolic disorders too,” says Dr Baruteau.

What are the researchers’ credentials?

“Throughout this research, I will be supported by internationally renowned supervisors, based at world-class institutions,” says Dr Baruteau. “Thinking of the children, and families, who are affected by metabolic disease motivates me strongly to succeed. I am grateful to Action Medical Research for helping me make a difference to their lives.”

*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.


1. Campeau PM et al. A 25-year longitudinal analysis of treatment efficacy in inborn errors of metabolism. Molecular genetics and metabolism 2008; 95:11-6.

2. Sanderson S et al. The incidence of inherited metabolic disorders in the West Midlands, UK. Archives of disease in childhood 2006; 91:896-9.

Project LeaderDr Julien Baruteau MD
Project TeamDr Simon Waddington PhDDr Steve Howe PhDDr P Gissen PhD, MD, FRCPHDr Philippa Mills PhD
Project LocationGreat Ormond Street Hospital, London
Project Location OtherInstitute for Women's Health, University College LondonInstitute of Child Health, University College LondonLaboratory for Molecular Cell Biology, University College London
Project duration2.5 years
Date awarded13 February 2013
Project start date14 October 2013
Project end date30 September 2017
Grant amount£198,473
Grant codeGN2137


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