From novel targets to potential therapies: development of antisense oligonucleotides for progressive supranuclear palsy

We developed candidate therapeutics for PSP using ASOs that silence novel therapeutic targets discovered in our systems based cross-species screening. We showed that our ASOs have low toxicity and confirmed target engagement at both mRNA and protein levels in vitro. The results suggest a favorable preclinical profile of our ASO leads that warrants additional investigations. Importantly, PSP shares congruent pathophysiological changes with other tauopathies, such as Alzheimer's disease. These common perturbed pathways indicate that our ASOs can be potentially repurposed for multiple neurodegenerative tauopathies.

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Publication Details

Journal
Alzheimer s & Dementia
Published
2025-12-01
DOI
https://doi.org/10.1002/alz70859_100315
Primary Topic
Parkinson's Disease Mechanisms and Treatments
Type
article
Field-Weighted Citation Impact
0.00
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article

From novel targets to potential therapies: development of antisense oligonucleotides for progressive supranuclear palsy

Pablo Martínez, Adriana O. Mitchell, Dennis W. Dickson, Keiji Kawatani et al.
Alzheimer s & Dementia
Parkinson's Disease Mechanisms and Treatments
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From novel targets to potential therapies: development of antisense oligonucleotides for progressive supranuclear palsy

Pablo Martínez, Adriana O. Mitchell, Dennis W. Dickson, Keiji Kawatani, Joseph S. Reddy, Takahisa Kanekiyo, Cristian A Lasagna Reeves, John F. Crary, Mariet Allen, Zachary Quicksall, Kristen Whitney, Jeremiah Bergman, Grace A. Selecky, Nilüfer Ertekin‐Taner, Jianna Tan, Yuhao Min, Thuy T. Nguyen, Xue Wang, Katie D. Sotelo
article en

Abstract

We developed candidate therapeutics for PSP using ASOs that silence novel therapeutic targets discovered in our systems based cross-species screening. We showed that our ASOs have low toxicity and confirmed target engagement at both mRNA and protein levels in vitro. The results suggest a favorable preclinical profile of our ASO leads that warrants additional investigations. Importantly, PSP shares congruent pathophysiological changes with other tauopathies, such as Alzheimer's disease. These common perturbed pathways indicate that our ASOs can be potentially repurposed for multiple neurodegenerative tauopathies.

Alzheimer s & DementiaVol. 21(S5)
Allen Institute for Brain Science (US), Alzheimer's Drug Discovery Foundation (US), WinnMed (US), Mayo Clinic in Florida (US), Indiana University School of Medicine, Indiana University – Purdue University Indianapolis (US), Icahn School of Medicine at Mount Sinai (US)
Good health and well-being
Openalex Percentile: Top 31%
Parkinson's Disease Mechanisms and Treatments
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