New Therapeutic Strategies for Lewy Body Dementias
Overview
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This article reviews current treatment strategies and recent advances for the Lewy body dementias (LBDs). Current available symptom treatment strategies are based on monoaminergic, cholinergic and glutaminergic neurotransmitter systems. Relatively robust evidence exists for cholinesterase inhibitors for cognitive impairment in LBD and in Parkinson's disease for antidepressants, clozapine and recently pimavanserin for psychosis. interpidine (RVT 101) and nelotanserin are currently under investigation. Non-pharmacological interventions, such as cognitive stimulation, physical exercises and neuromodulation strategies, may be useful in Parkinson's disease but have not yet been tested in dementias. Disease-modifying approaches are aimed at preventing, slowing or ameliorating the production, aggregation and deposition of pathological proteins, including immunotherapy targeting α-synuclein and an ongoing trial using ambroxol which increases glucocerebrosidase activity to lower the levels of the protein alpha-synuclein. Other disease-modifying clinical trials are using agents to augment insulin signalling, stem cell therapy, reducing amyloid pathology and gene therapy.
Caramelli P, Marinho V, Laks J, Coletta M, Stella F, Camargos E Dement Neuropsychol. 2022; 16(3 Suppl 1):88-100.
PMID: 36533154 PMC: 9745994. DOI: 10.1590/1980-5764-DN-2022-S106PT.
OBrien J, Chouliaras L, Sultana J, Taylor J, Ballard C Alzheimers Res Ther. 2022; 14(1):169.
PMID: 36369100 PMC: 9650797. DOI: 10.1186/s13195-022-01103-7.
The Role of Glial Mitochondria in α-Synuclein Toxicity.
Jeon Y, Kwon Y, Jo M, Lee S, Kim S, Kim H Front Cell Dev Biol. 2020; 8:548283.
PMID: 33262983 PMC: 7686475. DOI: 10.3389/fcell.2020.548283.
Bitencourt A, Campos R, Cline E, Klein W, Sebollela A Int J Mol Sci. 2020; 21(23).
PMID: 33255488 PMC: 7727795. DOI: 10.3390/ijms21238920.
Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials.
Goldman J, Forsberg L, Boeve B, Armstrong M, Irwin D, Ferman T Alzheimers Res Ther. 2020; 12(1):137.
PMID: 33121510 PMC: 7597002. DOI: 10.1186/s13195-020-00703-5.