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Neurodegeneration

Senolytic therapy for Alzheimer’s disease

Nature Medicine volume 29, pages 2409–2411 (2023)Cite this article

As the search for new and better treatments for Alzheimer’s disease continues, a phase 1 proof-of-concept study evaluating senolytic therapy breaks new ground.

Recent phase 3 Alzheimer’s disease trials using anti-amyloid antibodies have demonstrated a significant slowing of cognitive decline and disease progression (based on selected neurodegenerative biomarkers). Although this progress constitutes an important landmark in the field, the clinical effects are still modest and the risk–benefit balance—in the context of treatment-induced brain atrophy and risk for brain edema — will continue to be evaluated. The search for additional therapeutic approaches therefore remains a high priority. As an alternative or adjunctive approach to direct targeting of pathogenic drivers (such as oligomeric amyloid-β or tau), modulation of other fundamental biological mechanisms of neurodegeneration may render synapses resilient, while concomitantly dampening a spectrum of Alzheimer’s pathologies1. Aging continues to be recognized as the largest risk factor for Alzheimer’s disease, which has sparked widespread interest in targeting age-related mechanisms — particularly cellular senescence. In this issue of Nature Medicine, Orr et al.2 report results of SToMP-AD, the first clinical trial to evaluate a senolytic therapy (designed to remove senescent cells within the brain) in patients with early-stage Alzheimer’s disease.

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Fig. 1: Effects of senolytic therapy in Alzheimer’s disease.

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Authors and Affiliations

  1. Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA, USA

    Frank M. Longo

  2. Veteran’s Administration Health Care System, San Francisco, CA, USA

    Stephen M. Massa

  3. Department of Neurology, University of California San Francisco, San Francisco, CA, USA

    Stephen M. Massa

Authors
  1. Frank M. Longo
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  2. Stephen M. Massa
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Correspondence to Frank M. Longo.

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Competing interests

F.M.L. and S.M.M. are listed as inventors on patents relating to small molecule, therapeutic approaches for Alzheimer’s and other neurodegenerative diseases and are entitled to royalties. F.M.L. is a principal of, and has a financial interest in PharmatrophiX, a company that has licensed several of these patents.

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Longo, F.M., Massa, S.M. Senolytic therapy for Alzheimer’s disease. Nat Med 29, 2409–2411 (2023). https://doi.org/10.1038/s41591-023-02541-y

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