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Neurodegenerative disease

Silencing tau to treat early Alzheimer’s disease

Nature Medicine (2023)Cite this article

An antisense oligonucleotide therapy substantially reduced tau expression in a phase 1b trial; whether this translates to clinical improvement remains to be seen, but it could have far-reaching implications for neurodegenerative diseases more broadly.

The recent accelerated approval of aducanumab and lecanemab by the US Food and Drug Administration (FDA) heralds a new era in Alzheimer’s disease (AD) therapeutics. Aducanumab and lecanemab are monoclonal antibodies that target aggregated amyloid-β (Aβ) and robustly lower amyloid plaque load, as assessed by Aβ positron emission tomography (PET)1,2. Although the clinical outcomes of two phase 3 studies of aducanumab yielded conflicting results1, a recent phase 3 study of lecanemab demonstrated unequivocal slowing of cognitive and functional decline in patients with early symptomatic AD2. Yet despite this exciting progress, the clinical benefits of lowering Aβ are modest, and there remains a great need for additional therapeutic targets that will more profoundly change the trajectory of AD.

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Fig. 1: Tau PET across the AD continuum.

Claire Yballa and Daniel Schonhaut, University of California San Francisco

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Authors and Affiliations

  1. Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA

    Peter A. Ljubenkov & Gil D. Rabinovici

  2. Department of Radiology & Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA

    Gil D. Rabinovici

Authors
  1. Peter A. Ljubenkov
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  2. Gil D. Rabinovici
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Corresponding author

Correspondence to Gil D. Rabinovici.

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Competing interests

P.A.L. receives research search support from the National Institute on Aging of the US National Institutes of Health and from the Alzheimer’s Association Part the Cloud Partnership. He is the FDA investigational new drug sponsor for a clinical trial of a drug supplied by Biohaven. He has served as a clinical site primary investigator for trials sponsored by Woolsey, Alector, Transposon and AbbVie. He also currently serves as a clinical site sub-investigator for clinical trials sponsored by Lilly, Eisai and Biogen. G.D.R. receives research support from the US National Institutes of Health, the Alzheimer’s Association, the American College of Radiology, the Rainwater Charitable Foundation and the Alliance for Therapies in Neuroscience. He has served as a paid scientific advisor to Alector, Eli Lilly, GE Healthcare, Genentech, Johnson & Johnson Merck, and Roche.

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Ljubenkov, P.A., Rabinovici, G.D. Silencing tau to treat early Alzheimer’s disease. Nat Med (2023). https://doi.org/10.1038/s41591-023-02357-w

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