Table 2.

Summary of agents prioritised for repurposing for LBD by the international Delphi panel

Proposed candidate	Suggested mechanisms of action	Summary of evidence	Future work required
Ambroxol	-Neuroprotective effects through upregulating GCase	-Reduction of α-synuclein pathology and improved mitochondrial function -Penetrates the CSF and engages the treatment target in humans	-Pharmacokinetics -Better understanding of mechanisms -Phase 2 work needed with CNS or CSF biomarkers to support target engagement
Nilotinib/bosutinib	-Increases the clearance of α-synuclein, amyloid, hyperphosphorylated tau -Stimulates autophagy -Anti-inflammatory effect -Rescues synaptic dysfunction	-Safe, well tolerated -Increase in dopamine metabolites in the CSF -Reduction of CSF α-synuclein oligomers and hyperphosphorylated tau -Worsening of motor scores	-Await results of ongoing trials -Safety work, especially in older adults and QTc prolongation
Liraglutide/exenatide	-Decreases astrocyte and microglial activation -Decreases chronic inflammation and lipid peroxidation -Suppresses the apoptosis pathway -Increases autophagy-related protein expression -Reduces free oxygen species	-Improvements in off-medication scores on part 3 of the MDS-UPDRS -Lower rate of PD compared to the use of other antidiabetic drugs	-Phase 2 work needed with CNS or CSF biomarkers to support target engagement in LBD
Candesartan/telmisartan	-Inhibits the expression of TLR2 and TLR4 -Reverses the activated proinflammatory phenotype of primary microglia -Reduces TNF-α levels	-Improvement of motor deficits in animal models -Reduction in levels of α-synuclein and attenuation of ER stress-triggered neuronal apoptosis -Improvement of cognitive performance in various cohorts	-More preclinical evidence and studies on whether they cross the BBB -Additional epidemiological evidence -Phase 2 trials in LBD
Metformin	-Prevents α-synuclein phosphorylation and aggregation -Prevents astroglia and microglia activation -Improves cell survival and promotes autophagy	-Reduction of amyloid beta secretion and tau phosphorylation -Improves cognitive performance in animal models. -Improves motor impairments in PD animal models -Improves verbal learning and memory in amnestic MCI.	-Phase 2 research needed with CNS or CSF biomarkers to support target engagement in LBD -Prodromal studies in enriched RBD may have a direct relevance for LBD
Fasudil	-Promotes the degradation of α-synuclein via autophagy through the JNK 1/Bcl-2/beclin 1 pathway -Dilates cerebral vessels -Inhibits the release of intracellular calcium	-Reduction of phosphorylated α-synuclein -Improves motor deficits in various animal models of PD -Rescues cognitive deficits, reduced acetylcholinesterase activity and oxidative stress in AD animal models	-Need clinical/pharmacokinetic studies to CNS penetration -Phase 1 clinical studies

All citations referring to the findings summarised in Table 2 are provided in the main body of the manuscript

AD Alzheimer’s disease, BBB blood-brain barrier, Bcl2 B-cell lymphoma 2 protein, CSF cerebrospinal fluid, CNS central nervous system, ER endoplasmic reticulum, GCase glucocerebrosidase, JNK Jun N-terminal protein kinase 1, LBD Lewy body dementia, MCI mild cognitive impairment, PD Parkinson’s disease, RBD REM-sleep behavioural disorder, TLR2 Toll-like receptor 2, TNF-α tumour necrosis factor alpha, MDS-UPDRS Movement Disorder Society Unified Parkinson’s Disease Rating Scale