Jonathan R. Greene

Blocking somatic repeat expansion and lowering huntingtin via RNA interference synergize to prevent Huntingtons disease pathogenesis in mice

This study shows that combining RNAi to silence MSH3 and HTT reduces huntingtin inclusions and restores gene expression in HD mice.

Lowering the HTT1a transcript as an effective therapy for Huntingtons disease

The paper shows that lowering HTT1a transcript levels delays molecular and neuropathological phenotypes in a Huntington's disease mouse model.

A CAG repeat threshold for therapeutics targeting somatic instability in Huntington's disease

This study shows that reducing MSH3 in Huntington's disease mouse models prevents somatic CAG repeat expansion but does not accelerate disease onset, suggesting somatic expansion may not be required for pathogenesis.

Mutant HTT protein decreases with CAG repeat expansion: implications for therapeutics and bioassays.

The paper shows that mutant HTT levels decrease with CAG repeat expansion, suggesting therapeutic strategies should target HTT1a instead of full-length HTT.

Benefits of global mutant huntingtin lowering diminish over time in a Huntington's disease mouse model

This study shows that moderate global lowering of mutant Huntingtin in a HD mouse model delays some deficits but benefits diminish over time, suggesting long-term mHtt lowering may be needed for sustained benefit.