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Lewy Body Dementia: An Overview of Promising Therapeutics

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Abstract

Purpose of Review

Lewy body dementia (LBD) encompasses dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). This article will emphasize potential disease-modifying therapies as well as investigative symptomatic treatments for non-motor symptoms including cognitive impairment and psychosis that can present a tremendous burden to patients with LBD and their caregivers.

Recent Findings

We review 11 prospective disease-modifying therapies (DMT) including four with phase 2 data (neflamapimod, nilotinib, bosutinib, and E2027); four with some limited data in symptomatic populations including phase 1, open-label, registry, or cohort data (vodabatinib, ambroxol, clenbuterol, and terazosin); and three with phase 1 data in healthy populations (Anle138b, fosgonimeton, and CT1812). We also appraise four symptomatic therapies for cognitive impairment, but due to safety and efficacy concerns, only NYX-458 remains under active investigation. Of symptomatic therapies for psychosis recently investigated, pimavanserin shows promise in LBD, but studies of nelotanserin have been suspended.

Summary

Although the discovery of novel symptomatic and disease-modifying therapeutics remains a significant challenge, recently published and upcoming trials signify promising strides toward that aim.

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Papers of particular interest, published recently, have been highlighted as: •• Of major importance

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Authors and Affiliations

  1. Memory Disorders Division, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 213 Quarry Road, Palo Alto, CA, 94305, USA

    Irina A. Skylar-Scott & Sharon J. Sha

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  1. Irina A. Skylar-Scott
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  2. Sharon J. Sha
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ISS authored the original and subsequent manuscript drafts. SJS reviewed and edited the manuscript.

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Correspondence to Irina A. Skylar-Scott.

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Conflict of Interest

I.S.S. has received funding for clinical trials research from Eli Lilly, Eisai, Biogen, Janssen, Novartis, Alector, AbbVie, Genentech/Roche, Cortexyme, UCB Biopharma, and Alzheon.

S.J.S. has received consulting fees/honoraria from Biogen, Guidepoint Global, ExpertConnect, UpToDate, ReachMD, and Forefront Collaborative; and funding for research from Biogen, Janssen, Genentech, Novartis, Eisai, and Eli Lilly.

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Skylar-Scott, I.A., Sha, S.J. Lewy Body Dementia: An Overview of Promising Therapeutics. Curr Neurol Neurosci Rep 23, 581–592 (2023). https://doi.org/10.1007/s11910-023-01292-0

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