The polyglutamine (polyQ) diseases are a group of neurodegenerative disorders caused by expanded cytosine-adenine-guanine (CAG) repeats encoding a long polyQ tract in the respective proteins. To date, at least nine polyQ disorders have been described, see bellow for a list. Among them Huntington’s disease (HD) is the most widespread.
Currently, the standard of care of such disorders is focused on symptomatic treatments as no effective therapeutic interventions aimed at the treatment or prevention of polyQ diseases exist. This calls for an urgent need of innovative therapeutic strategies.
We have identified a number of novel therapeutic factors capable of reducing the toxicity of mutated proteins causing polyQ diseases. Their administration to both in vitro and in vivo model systems of HD via state-of-the-art gene therapy delivery systems resulted in amelioration of the detrimental effects of the mutant HTT gene, i.e., in reduced cell death, oxidative stress, transcriptional alterations, and alleviated motor deficit.