Lithium as a disease-modifying agent for prion diseases

Abstract

Prion diseases still remain incurable despite multiple efforts to develop a treatment. Therefore, it is important to find strategies to at least reduce the symptoms. Lithium has been considered as a neuroprotective agent for years, and the objective of this preclinical study was to evaluate the efficacy of lithium delivered as a water-in-oil microemulsion (Aonys®). This delivery system allows using low doses of lithium and to avoid the toxicity observed in chronic treatments. C57BL/6J mice were intracranially inoculated with ME7 prion-infected brain homogenates and then were treated with lithium from day 90 post inoculation until their death. Lithium was administered at traditional doses (16 mg/kg/day) by the gavage route and at lower doses (40 or 160 µg/kg/day; Aonys®) by the rectal mucosa route. Low doses of lithium (Aonys®) improved the survival of prion-inoculated mice, and also decreased vacuolization, astrogliosis, and neuronal loss compared with controls (vehicle alone). The extent of the protective effects in mice treated with low-dose lithium was comparable or even higher than what was observed in mice that received lithium at the traditional dose. These results indicate that lithium administered using this innovative delivery system could represent a potential therapeutic approach not only for prion diseases but also for other neurodegenerative diseases.

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“…Lithium also promoted a neuroprotective effect on GrDG, CA1, and CA3, reducing neurodegeneration and preserving neuronal density. C57Bl/6 animals with induced neurodegeneration and a transgenic mouse model of AD also presented increased neuronal density after treatment with lithium (Nunes et al, 2015 ; Relaño-Ginés et al, 2018 ). The animals treated with the combined strategies in this study also presented neuroprotection, but this combination was not more effective than the treatments alone.…”

Microdose lithium reduces cellular senescence in human astrocytes - a potential pharmacotherapy for COVID-19?

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Polyampholyte-Based Synthetic Chaperone Modulate Amyloid Aggregation and Lithium Delivery

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