Understanding the cause of ARSACS - Ataxia UK

Understanding the cause of ARSACS

Post Published: December 15, 2022

ARSACS is a rare inherited ataxia caused by mutations in a gene called the SACS gene, which is responsible for producing the sacsin protein. In people with ARSACS, the sacsin protein is not functional. However, it is not entirely known why this causes ARSACS. Researchers at Queen Mary University of London and the University of North Carolina, funded in part by Ataxia UK, recently published a paper describing their approach to better understand why loss of the sacsin protein causes ARSACS.

In this project, the researchers experimentally removed the sacsin protein from cells in the lab, and looked at the changes this caused in the cells. They saw a number of changes to the structure and function of the cells, and were therefore able to identify which processes sacsin is involved in. They confirmed that some of these changes were also seen in a mouse model of ARSACS. The image below shows brain samples taken from a healthy mouse (‘Wild Type’, left) and an ARSACS mouse (right). Some of the proteins in the brain cells have been dyed so they show in colour. The protein dyed green is involved in maintaining the structure of the cells, and clear differences can be seen between the two samples.

These processes are very complex, and they interact with one another, so it is difficult to identify which are most relevant for ARSACS. However, this work has raised a lot of possibilities to explore. Targeting these processes could be a potential treatment option for ARSACS in the future.

The research teams at Queen Mary University of London and the University of North Carolina started this work independently. When they realised they were working on similar projects, they joined forces to complete the work. The result is this thorough study of the role of sacsin, and shows that collaboration between researchers can be extremely beneficial.

Dr Lisa Romano, who contributed to this work during her PhD, which was part-funded by Ataxia UK said: “In this work,  we combined expertise and resources across different institutions to expand the breadth of ARSACS research. Our research demonstrates how unbiased cellular biology profiling can lead to discoveries that change our understanding of a disease. I have to say that ataxia is a very collaborative field, and this is very inspiring specially for young investigators like myself.”

Whilst working on this project, Dr Romano met her current mentor, Dr Laura Ranum. After successfully completing her PhD, Dr Romano started working in Dr Ranum’s lab, which is also focused on understanding the ataxias. This shows that funding scientists early in their career can encourage fantastic researchers such as Dr Romano to stay within the ataxia research field.

We wrote about this project in the Ataxia Magazine in Autumn 2020, Issue 211. The work has now been published in the scientific journal Cell Reports.

Read the full paper here.

Read a press release about the article here.

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