Metabolic Diseases | Action Medical Research | Children's Charity | Children's Charity

Metabolic diseases: hope of new treatments

First published on 18 February 2010

Updated on 25 March 2014

What did the project achieve?

“We have made important discoveries that could have a major impact on how children with four rare and devastating diseases might be treated in the future,” says Dr Emyr Lloyd-Evans, from the University of Cardiff, who led this research with Professor Fran Platt of the University of Oxford.

The diseases in question tend to begin during childhood, causing severe and distressing problems including birth defects, learning disabilities, movement difficulties, dementia and blindness. They are called Smith-Lemli-Opitz syndrome (SLOS), Mucolipidosis type IV (MLIV) and Niemann-Pick disease type C1 and C2 (NPC).

Sadly, children with these diseases can become severely disabled and some lose their lives. There is no cure, but a drug called miglustat slows progression in NPC.

“We have identified disease processes involved in these four illnesses,” says Dr Lloyd-Evans. “In particular, we’ve found that changes in calcium levels inside special compartments within cells, called lysosomes, play a central role. We have also discovered that the drug miglustat partly works by altering those calcium levels.”

“These are important findings, because they tell us that other drugs that alter calcium levels might also benefit children with these diseases,” continues Dr Lloyd-Evans. “We are currently testing several possible new treatments in the laboratory.”

This research was completed on 3 January 2013

Researchers are searching for possible new drugs to treat three rare but devastating inherited diseases that are typically diagnosed during childhood – Smith-Lemli-Opitz Syndrome (SLOS), Mucolipidosis type IV (MLIV) and Niemann-Pick disease type C (NPC). These three diseases can cause severe problems, including birth defects, learning disabilities, movement difficulties, dementia and blindness. Sadly, some children die. The researchers hope their work will eventually lead to new treatments that can reduce the children’s suffering and save their lives.

What's the problem and who does it affect?

Devastating diseases of childhood

The researchers are trying to help children with three inherited, metabolic diseases called Smith-Lemli-Opitz Syndrome (SLOS), Mucolipidosis type IV (MLIV) and Niemann-Pick disease type C (NPC).

Though symptoms vary considerably, children with SLOS are often born with birth defects, including cleft palates, webbing between their toes and heart malformations. They go on to have learning disabilities and behaviour problems, with many being autistic. They also tend to have weak muscle tone, difficulties feeding and retarded growth.

Babies with NPC usually seem normal at birth, but develop a range of problems including difficulties swallowing, a slow loss of speech, increasingly poor muscle control and a progressive decline in intellectual ability, which causes symptoms that are similar to Alzheimer’s disease.

During the first year of life, children with MLIV tend to be late to reach developmental milestones such as sitting, standing, walking and grasping objects. Their language skills and their control of their movement normally progress no further than those of a typical 15-month-old. The children’s eyesight gradually deteriorates, with many sufferers becoming blind by their teens.

There is no cure for any of these diseases, although a drug called miglustat slows disease progression in NPC. Sadly, NPC and SLOS often prove fatal. New treatments are desperately needed for these devastating diseases.

What is the project trying to achieve?

Seizing on a common link

The researchers have discovered that children with SLOS, NPC and MLIV all have alterations in the way calcium is released from special compartments in their cells, called lysosomes.

Lysosomes are the cell’s recycling centres and calcium plays an important role within cells, by acting as a messenger. In children with all three diseases, lysosomes cannot recycle waste materials properly. Fatty molecules therefore accumulate, causing disease.

The fact that SLOS, NPC and MLIV all share this common disease mechanism suggests that it might be possible to develop a new treatment that benefits children with all three diseases. The researchers are trying to do just that.

The work is beginning in the laboratory, where the researchers are characterising the nature of the calcium defect in more detail and investigating the effects of several potential drugs, including vitamin D3 and a small molecule called miglustat, which is already used to slow disease progression in NPC.

What are the researchers' credentials?

Project LeaderProfessor F Platt BSc PhD
Project team
  • Dr Emyr Lloyd-Evans DPhil
LocationDepartment of Pharmacology, University of Oxford
Duration3 years
Grant awarded18 November 2009
Start date4 January 2010
End date3 January 2013
Grant amount£119,636.00
Grant codeSP4524, GN1766

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The research team’s priority in this project is to develop therapies for three rare but devastating genetic diseases. Most pharmaceutical companies have little interest in developing therapies for rare diseases, meaning the responsibility falls to University researchers and charities like Action Medical Research.

The researchers are internationally recognised experts in diseases that affect the cell’s recycling centre – the lysosome – and have an established track record of developing therapies for lysosomal disorders, including a drug called miglustat for an illness called type I Gaucher disease and for NPC.

The regulation of calcium in the lysosome has long been a major focus of the team’s research and the department in which they work, and this project extends that focus to the diseases that result when calcium regulation goes wrong.

The researchers are based at the Department of Pharmacology, Oxford University. Together with the Department of Physiology, Anatomy and Genetics, the department was ranked top in the UK in pre-clinical and human biological sciences in 2008’s Research Assessment Exercise, a peer-reviewed evaluation of institutions that offer higher education.

Who stands to benefit from this research and how?

Working towards new treatments

The researchers hope their work will eventually benefit everyone with SLOS, NPC and MLIV. All three diseases tend to begin during childhood, though NPC and SLOS can also be diagnosed in adults. Around 100 people have NPC in the UK and several hundred are estimated to have SLOS.1,2 The number with MLIV is not known.

The researchers’ ultimate aim is to develop new treatments for all three diseases. If the results in the laboratory are promising, they plan to work towards clinical trials as quickly as possible.

All three diseases can have a devastating impact on sufferers and their families. As the children can be severely disabled, the family home often needs extensive modifications. The support of GPs and nurses is needed at home, respite care can be essential to help parents cope, and the children’s many and varied symptoms mean they often need to see several different hospital consultants. Sadly, some children eventually have to go into a hospice.

Effective new treatments could transform lives for the better and bring large cost savings to the public and charitable sectors.


  1. Imrie J, Dasgupta S, Besley GT, Harris C, Heptinstall L, Knight S, Vanier MT, Fensom AH, Ward C, Jacklin E, Whitehouse C, Wraith JE. The natural history of Niemann-Pick disease type C in the UK. J Inherit Metab Dis 2007; 30 (1):51-9. Epub 2006 Dec 11.
  2. Porter FD. Smith–Lemli–Opitz syndrome: pathogenesis, diagnosis and management. European Journal of Human Genetics 2008; 16 (5): 535–541; doi:10.1038/ejhg.2008.10; published online 20 February 2008.
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