mHTT translation inhibitors

Huntington's disease

Huntington’s disease belongs to a group of diseases called repeat associated diseases. Recent scientific discoveries point to malfunctions of the translation machinery as an underlying cause of this disease as well as for other repeat associated diseases.

Read more about Repeat associated diseases and Anima’s discovery program using novel technology to discover compounds that correct translation malfunctions.

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 (repeat 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 40, 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 our platform, we found that there is a general translation defect in cells expressing mutant HTT. We discovered and are in the process of validating highly selective mutant HTT translation inhibitors. Our compounds act on reducing mutant Huntingtin protein without affecting the wildtype protein.

  • High throughput screening using Anima’s proprietary platform
    Multiple chemically diverse series identified
  • Specifically reduce mHTT protein translation and accumulation
    Dose-response activity shown with activity at the uM levels in cell-based assays
  • Compounds demonstrated selectivity toward mHTT
    - Do not affect global and housekeeping protein synthesis
    - Selective to mHTT with no effect on wtHTT
  • Next Compounds Optimization