Holly B. Kordasiewicz

This paper develops a VHH-Fc fusion protein to deliver siRNAs and ASOs across the BBB in rodents and NHPs, showing that binding affinity, DAR, and conjugation site affect delivery efficiency.

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 evaluates the analgesic effects of intrathecal NaV 1.7 antisense oligonucleotides in rats, showing reduced channel binding and pain behaviors with concentration-dependent knock-down of Scn9a mRNA.

This study shows that reducing EMC10 levels in 22q11.2 deletion syndrome models improves cognitive function and sustains benefits for over two months.

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

This study shows that reducing GPNMB in progranulin-deficient myeloid cells impairs lysosomal function and immune responses, suggesting GPNMB is essential for maintaining immune homeostasis.

This study characterizes an acute sedation response caused by phosphorothioate ASOs after CNS delivery, showing it is sequence-, dose-, and chemistry-dependent and can be mitigated.

The paper characterizes a transient neurobehavioral response to high-dose oligonucleotide delivery in the CNS and provides a framework to mitigate it through magnesium supplementation.

This study shows that reducing mutant Lrrk2 in macrophages decreases lysosomal tubule formation and pro-inflammatory responses, suggesting potential therapeutic benefits for LRRK2-related Parkinson's but possible immune system side effects.

The paper maps antisense oligonucleotide activity in the brain using single-cell transcriptomics in mice and macaques, showing widespread target suppression across cell types with varying durations.

This study shows that Gys1 antisense therapy reduces Lafora body formation and neuroinflammation in mouse models of Lafora disease.

The paper maps ASO distribution and activity in the CNS of rodents and NHP after central administration, showing widespread effects across cell types.

This study shows that increasing convective forces after intrathecal injection improves rostral distribution of therapeutic ASOs in the CNS of cynomolgus monkeys.

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 paper demonstrates that antisense oligonucleotides targeting SNCA reduce alpha-synuclein production, prevent pathology, and show translational potential in non-human primates.

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