Huntington’s disease

Assay Development
Hit Generation
Hit to lead
HuntingtinHuntington's disease

Three different PSM assays developed to monitor translation defects in cells expressing mutant Huntingtin: translation stalling, mutant huntingtin translation and activation of ribosome quality control.

Huntington’s disease (HD) is a dominantly transmitted neurodegenerative disorder with an average age at onset of 40 years. It is associated with extended repeats of glutamine (repeated of the trinucleotide CAG) in a protein called Huntingtin (HTT). Normally, the CAG segment is repeated 10 to 35 times within HTT, but when repeats are higher than 100, disease occurs. The exact mechanism which causes disease due to extended CAG repeats is unclear. Currently, there is no treatment that can stop or reverse the course of HD.

Using Anima’s PSM technology we show that there is a general translation defect in cells expressing mutant HTT, resulting in aberrant activation of the ribosome quality control machinery. We have developed three different assays which are ready to be screened towards the discovery of molecules which will alleviate translation arrest in extended-HTT expressing cells.

Our discovery program is using our novel technology to discover compounds that may correct ribosome stalling, which we believe may be an underlying cause for the Huntington disease.