Christian Landles

This paper develops and validates recombinant monoclonal antibodies that selectively detect specific huntingtin neoepitopes, addressing variability in existing antibodies and enabling new research into huntingtin fragment cleavage mechanisms.

This study develops and evaluates two novel antibodies, 1B12 and 11G2, for more sensitive detection of HTT1a in Huntington's disease mouse models compared to the existing MW8 antibody.

This study compares allele-selective and non-allele-selective antisense oligonucleotides in HD mice, showing that targeting mutant HTT intron-1 reduces HTT1a and improves disease outcomes.

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

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

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.

The paper demonstrates that CRISPR-Cas9 nickase can contract CAG/CTG repeats in patient-derived cells and improve molecular and behavioral phenotypes in Huntington's disease.

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

This study uses correlative light and electron microscopy to show that mutant huntingtin accumulates in endolysosomal organelles in presymptomatic Huntington's disease, altering endolysosomal homeostasis.

This study identifies TBK1 as a kinase that phosphorylates mutant huntingtin, reduces its aggregation and toxicity in multiple HD models.