Towards a personalised treatment for SCA1

In 2022, Ataxia UK awarded funding to Dr Francesca Salvatori at the University of Ferrera in Italy, for a project focused on SCA1. 

Previous work 

SCA1 is caused by the production of a toxic version of the ataxin-1 protein. In previous work, Dr Salvatori and her team showed that they could target the SCA1 gene to reduce the expression of the ataxin-1 protein. However, people with SCA1 have two SCA1 genes – the one that produces the toxic ataxin-1 protein, and another one that produces healthy ataxin-1 protein. The method used previously by this group reduced the expression of both the healthy and the SCA-1 causing ataxin-1 protein. Healthy ataxin-1 has a role in the body, so reducing this could have negative consequences. To avoid, this, they wanted to develop a similar technique which would allow them to only reduce the expression of the SCA-1 causing ataxin-1 protein. To do this, they designed personalized treatment for 6 people with SCA1, and tested this method on cells taken from these volunteers. 

Ataxia UK-funded research plans 

To determine how well this technique works, the researchers needed a way to measure the SCA1-causing ataxin-1 protein. A common way to measure proteins in the lab is to label them with another protein, called an antibody. Antibodies specifically label one type of protein, and are easy to measure. Using this technique, the researchers planned to measure both the healthy and the SCA1-causing ataxin-1 protein. If the treatment was successful, they would see a decrease in SCA1-causing ataxin-1 protein, and no decrease in the healthy SCA1 protein. 

The funding from Ataxia UK was to go towards developing an antibody that could distinguish between the SCA1-causing protein, and the healthy protein (i.e. it would only label SCA1-causing protein, thereby allowing them researchers to accurately measure the amount of SCA1-causing protein). Producing this antibody turned out not to be possible. The researchers used the funding to continue the SCA1 project in a different way. 

Alternative method 

The researchers did find a way to measure the healthy and SCA1-causing ataxin-1 protein. However, the method was not very accurate. Using this alternative method, they showed that they can target the SCA1-causing protein, leaving the healthy protein to be produced as normal. This gives the researchers reason to think that they might be able to target the SCA1-causing protein, but their way of measuring the results was not very accurate or reliable. 

Future plans 

Next, the researchers plan to test this method on a more relevant cell type.