Research Project

Novel biomarkers of oxidative stress in Friedreich’s ataxia 

Principal researchers: Prof Peter Clayton, Prof Philippa Mills, Dr Youssef Khalil and Prof Paola Giunti, UCL Great Ormond Street Institute of Child Health, and the Ataxia Centre, UCL Institute of Neurology (UK) 

Scientific Summary 

Niemann Pick Type C (NPC) is a rare condition which can cause ataxia. It is caused by mutations in one of two genes (NPC1 or NPC2), which are involved in the export of cholesterol from the lysosomes. Mutations in these genes leads to accumulation of unesterified cholesterol in the lysosomes. Lysosomes have an acidic pH and contain iron – features that favour an attack on the accumulating cholesterol by reactive oxygen species (ROS). This reaction leads to an increase in bile acids, which can be used to diagnose NPC. 

These researchers tested plasma levels of bile acids in 189 people with ataxia of unknown cause, attending the London Ataxia Centre. One of those tested who had increased levels of bile acids was subsequently diagnosed with Friedreich’s ataxia (FA). This led the researchers to ask whether oxidation of cholesterol by ROS could play a role of the pathogenesis of FA, or provide a marker of ROS damage. 

In this project, the researchers will measure plasma levels of specific bile acids in 50 people with FA and 50 controls to see if increased oxidation of cholesterol by ROS is a consistent finding in people with FA, and if there is any correlation with disease severity or treatment. 

Lay Summary  

Niemann Pick Type C (NPC) is a rare condition which can cause ataxia. In people with NPC, cholesterol in the cells reacts with an unstable molecule known as a reactive oxygen species (or ROS). This reaction produces specific bile acids. Levels of these bile acids in blood and urine can be measured, and raised levels can indicate that a person has NPC. 

These researchers have measured the level of specific bile acids in blood samples taken from 189 people with ataxia of unknown cause, attending the London Ataxia Centre. Some of the individuals tested had raised levels of bile acids. Genetic testing confirmed that one of the individuals had Friedreich’s ataxia (FA). 

We know that in FA, iron can accumulate in cells and lead to the production of ROS. This could lead to an increase in bile acids, as described above for NPC. These researchers think that measuring the level of bile acids in people with FA could be a good indicator of how progressed the condition is. 

In this project, the researchers will investigate whether bile acids are increased in other people with FA. They will also look at whether measuring the level of bile acids could be an indicator of the response to treatment for FA (known as a biomarker). Identification of biomarkers is very important for the design and success of clinical trials. 

For more support or information please contact:  
Ataxia UK, 12 Broadbent Close, London, N6 5JW 
Website: www.ataxia.org.uk.   
Helpline: 0800 995 6037 Tel: +44 (0)20 7582 1444   
Email: helpline@ataxia.org.uk.