Genetic code consists of the letters A, T, G and C. Both spinocerebellar ataxia type 3 (SCA3) and type 1 (SCA1) are caused by mutations in the Ataxin-3 and Ataxin-1 genes, respectively, that cause a part of their genetic code containing the letters ‘CAG’ to be repeated. This leads to the production of toxic ‘polyglutamine proteins’. SCA3 and SCA1 are therefore classed as ‘polyglutamine diseases’.

Researchers from BioMarin and Charles River Discovery Research Services have previously demonstrated in mouse models of Huntington’s disease that the amount of toxic polyglutamine protein can be decreased administering a ‘CAG repeat-targeting antisense oligonucleotide’. This works by targeting the repeated genetic code within the faulty genes and modifying it to stop it from making the toxic proteins.

Following their success with Huntington’s disease, the researchers have recently tested the same CAG repeat-targeting antisense oligonucleotide, named ‘(CUG)7’, in mouse models of SCA1 and SCA3 and in cells derived from human patients. They discovered that administering (CUG)7 significantly reduced the amount of mutant protein in the brains of both SCA3 and SCA1 mouse models.

These findings demonstrate the therapeutic potential of a single CAG repeat-targeting antisense oligonucleotide for SCA3 and SCA1, as well as supporting their broader use in polyglutamine diseases. View the full paper here.

Posted on 16/08/2019