SCA3 (also known as Machado-Joseph Disease) is caused by a genetic mutation in the ATXN3 gene. It is thought to be the most prevalent SCA worldwide, and as with the other SCAs there is not yet any effective treatment for SCA3.
Genes contain instructions for how to make proteins. Therefore if there is a mutation in the gene, the instructions are incorrect and the protein is not made properly. This is the case with SCA3. Due to the mutation, the ATXN3 protein becomes stickier than usual and attaches to other sticky ATXN3 proteins. This leads to the formation of clumps of ATXN3 protein, known as aggregates. It is these aggregates that start the chain of events which leads to the symptoms of SCA3.
A recent study led by a group of researchers in Portugal tested the effect of trehalose on an animal model of SCA3. Trehalose is a naturally occurring substance found in many organisms from plants to bacteria. Trehalose has been shown to slow disease progression in other conditions caused by protein aggregates, but until now no results have been published looking at trehalose in an animal model of SCA3.
In this study, the researchers showed that trehalose decreased the number of protein aggregates in a cell model of SCA3. They then tested it in an animal model of SCA3. Their results show that motor function (movement) of the animals was improved following treatment with trehalose.
Whilst this is very encouraging, the authors do note that the effect of trehalose is quite small. Other approaches being studied in laboratories, such as gene therapy, are much more effective. This could indicate that trehalose could be a useful treatment to be used alongside other treatments that are currently in development.
Trehalose is currently being developed for the treatment of SCA3 by Seelos Therapeutics.
Read the full research article here.
Update on March 30th, 2023:
Seelos have announced that they are pausing their phase 2/3 study of Trehalose for SCA3, due to financial considerations. They have said this is not due to any data related to safety concerns or therapeutic effects.
