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Smith-Lemli-Opitz syndrome: working towards a new treatment

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What did the project achieve?

“We have uncovered some unexpected new aspects of the biology of SLOS which will help pave the way to better treatments in the future,” says Dr Emyr Lloyd-Evans of Cardiff University. “Our investigations have also led us towards an existing drug with exciting potential as a new treatment for children with the condition.”

Smith-Lemli-Opitz Syndrome (SLOS) is a rare, incurable inherited condition. Babies born with SLOS have a faulty gene that means that cells in their body can’t make cholesterol.  All affected children have an autism spectrum condition (ASC) and some are also born with other problems – such as cleft palates, learning disabilities and life-threatening heart conditions.

The only treatment currently available is to boost the amount of cholesterol in the child’s diet – but sadly, this isn’t very effective.

Dr Lloyd-Evans’ team has carried out a series of laboratory experiments to build on their previous discovery that cells from SLOS patients look identical to those from another rare inherited condition called Niemann-Pick C (NPC).

"Our results have uncovered the exact link between the biology of the two diseases at a molecular level – and because of this, we also now understand why cells from the diseases look similar and why dietary cholesterol treatment doesn’t work so well for children with SLOS,” says Dr Lloyd-Evans.

Dr Lloyd-Evans was also investigating whether any new therapies recently developed for NPC could also be beneficial for children with SLOS.

“In our laboratory experiments, we found that an existing drug can improve symptoms of SLOS – and importantly, we understand how it works,” says Dr Lloyd-Evans. “This improved understanding of the biology of SLOS takes us one step closer to finding an effective treatment for this rare, but potentially devastating disease.”

This research was completed on

Estimates suggest at least one in 60,000 newborn babies in the UK has a rare genetic disorder called Smith-Lemli-Opitz syndrome (SLOS).1 All of these babies have autism spectrum disorders and the most severely affected have birth defects, such as cleft palates, learning disabilities and life-threatening heart defects. There is no cure and no proven effective treatment. Recent discoveries suggest that two drugs might benefit children with SLOS. Dr Emyr Lloyd-Evans, of Cardiff University, is investigating this possibility in the laboratory.

What is the problem and who does it affect?

SLOS is a rare and often devastating illness with no cure and no treatment. It is thought to be the cause of a high number of miscarriages in Europe.2

Babies who do survive pregnancy are affected to varying degrees. “All children with SLOS have autism spectrum disorders,” explains Dr Lloyd-Evans, “which is the most significant problem for those who are mildly affected, causing difficulties interacting with other people and influencing performance at school. Children with the more severe form of the illness can have serious learning disabilities that affect all aspects of life, as well as birth defects such as small heads, cleft palates and extra fingers. Sadly, some children lose their lives to the condition, with heart defects being the major cause of death.”

SLOS results from a failure of the body to make its own cholesterol. “The only therapy that has typically been offered is to increase dietary cholesterol, which can be difficult, especially as cholesterol does not cross not into the brain,” says Dr Lloyd-Evans. “Unfortunately, a clinical study has shown that this therapy has little to no effect and so there is currently no viable treatment for SLOS, which is a great source of concern for families and doctors alike.”

What is the project trying to achieve?

Dr Lloyd-Evans is overseeing a range of laboratory studies with several important goals. He hopes to reveal more about the molecular processes that cause SLOS, develop new clinical tests for monitoring disease progression, assess the potential of two possible new treatments, and find out more about how one of the treatments works.

“We have recently discovered similarities between SLOS and another rare illness called Niemann-Pick C (NPC),” explains Dr Lloyd-Evans. “In NPC, cholesterol gets stuck inside a compartment within cells called the lysosome. We think that the same thing happens in SLOS, meaning therapies that work for children with NPC might also help children with SLOS. Treatment slows disease progression of NPC – if it could do the same for children with SLOS that would be a significant advance. Our laboratory work will provide the essential proof of principle that’s needed before clinical trials can begin in children with SLOS.”

What are the researchers’ credentials?

The highly skilled researchers in Dr Lloyd-Evans’ laboratory conduct world-leading research into the role of the lysosome in health and disease. They are currently developing therapies for a range of diseases that involve malfunction of the lysosome, which is commonly referred to as the recycling centre of cells.



  1. Ryan AK et al. Smith-Lemli-Optiz syndrome: a variable clinical and biochemical phenotype. J Med Genet 1998; 35(7):558-65.
  2. Nowaczyk MJ et al. DHCR7 mutation carrier rates and prevalence of the RSH/Smith-Lemli-Opitz syndrome: where are the patients? Am J Med Genet A 2006; 140(19): 2057-62.


Project Leader Dr Emyr Lloyd-Evans M.Bioch DPhil (Oxon)
Project Team Dr Helen Waller-Evans BSc DPhil (Oxon)
Project Location School of Bioscience, Cardiff University
Project duration 3 years
Date awarded 26 July 2012
Project start date 15 November 2012
Project end date 1 November 2016
Grant amount £173,809
Grant code GN2069
Acknowledgements This project is supported by a generous grant from The Henry Smith Charity


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