4.5 Review

Dementia with Lewy bodies: emerging drug targets and therapeutics

Journal

EXPERT OPINION ON INVESTIGATIONAL DRUGS
Volume 30, Issue 6, Pages 603-609

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/13543784.2021.1916913

Keywords

Clinical trials; dementia with Lewy bodies; drug repurposing; drug development; Lewy body dementia; Parkinson’ s disease; dementia; synucleinopathy; drug targets

Funding

  1. NIH COBRE [5P20GM109025]
  2. Keep Memory Alive Foundation
  3. NIH [P20 AG068054, R01AG059008]

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DLB is characterized by toxic accumulation of alpha-synuclein protein and shares features with PD and PDD, as well as overlaps with Alzheimer's disease. Treatments for DLB should not be solely duplicative of AD or PD, opening up numerous possibilities for disease-specific or repurposed therapeutic approaches.
Introduction: Dementia with Lewy bodies (DLB) is characterized by the toxic accumulation of alpha-synuclein protein inside neural cells; this results in neurodegeneration which is clinically accompanied by behavioral and psychological changes. DLB shares features with Parkinson's disease (PD) and Parkinson's disease dementia (PDD), but also overlaps neurochemically and pathologically with Alzheimer's disease. Symptomatic treatments for LBD differ in their effectiveness while disease-modifying and curative approaches are much needed. Areas covered: We explore emerging therapeutics for DLB through the lens of repurposing approved drugs and survey their potential for disease modifying actions in DLB. Given the complexity of DLB with multiple pathologies, potential therapeutic targets that could affect Lewy body pathology, or metabolism or neurotransmitters or immunomodulation were surveyed. We queried PubMed and ClinicalTrials.gov searches 2017-2020. Expert opinion: DLB is not simply aredux ofAD or PD; hence, treatments should not be exclusively duplicative ofAD or PD directed treatments. This opens amyriad of possibilities for therapeutic approaches that are disease specific or repurposed.

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