Jeffrey B. Carroll

VO659 reduces multiple neurotoxic mutant huntingtin proteins in Huntington's disease by targeting CAG repeats, while sparing wild-type HTT.

This study shows that reducing huntingtin in the liver causes inflammation and damage, highlighting safety concerns for HTT-lowering therapies.

scVIP models single-cell transcriptomes to predict phenotypes and infer trajectories in development and disease.

This paper demonstrates that antisense oligonucleotides targeting human ATN1 protect against DRPLA pathology in a fully humanized mouse model.

This study investigates how different HTT-lowering therapies affect somatic instability in HD mice, finding that transcriptional repression and CAG repeat binding reduce SI without lowering HTT levels.

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.

The paper identifies altered huntingtin-chromatin interactions in HD mouse models, linking them to transcriptional and epigenetic changes in striatal tissue.

The paper identifies genetic modifiers of Huntington's disease somatic CAG repeat instability using CRISPR-Cas9 in HD knock-in mice, revealing new therapeutic targets.

The paper analyzes genotypic and phenotypic data from 173 patients with nano-rare mutations to explore genotype-phenotype relationships and the potential for antisense oligonucleotide therapy.

This study shows that global Htt knockout in adult mice causes neurodegeneration and subcortical calcification but not pancreatitis, and increases neurofilament light chain levels.

This study uses single-nucleus RNA-seq to analyze striatal cell types in a Huntington’s disease mouse model, revealing dysregulated gene expression and cell identity loss across multiple cell types.

This study shows that reducing huntingtin protein levels decreases somatic instability in CAG-expanded loci in both mouse models and human neurons.

This study shows that lowering prion protein expression with ASOs is effective in treating prion disease across different strains, treatment times, and endpoints.

This study shows that reducing huntingtin in peripheral organs of HD mice does not improve central nervous system disease signs.

This study shows that B6.HttQ111/+ mice exhibit early transcriptional and proteostatic deficits before synapse loss and neurodegeneration in HD.

The paper builds genome-scale transcriptional regulatory networks for mouse and human striatum, identifying SMAD3 as a key regulator in Huntington’s disease.