Lithium as a disease-modifying agent for prion diseases.

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.

New hospital disinfection processes for both conventional and prion infectious agents compatible with thermosensitive medical equipment.

With the detection of prions in specific tissues in variant and sporadic Creutzfeldt-Jakob diseases, efficient decontamination for human transmissible spongiform encephalopathy (TSE) agents, that is compatible with medical equipment, has become a major issue. We previously described the cleavage of prions on exposure to copper (Cu) and hydrogen peroxide (H(2)O(2)) and have used this property to develop efficient prion decontamination processes. To validate this approach, in-vitro assays on genuine human and animal prions using both brain homogenates and steel wires to mimic contamination of medical equipment were conducted. In-vivo experiments using steel wire in the hamster 263 K model were then used to evaluate the effect on prion infectivity. Assays on classical pathogens following international norms completed these prion experiments. In-vitro data confirmed the full decontamination efficacy of H(2)O(2)/Cu on different TSE strains. Combination of Cu with peracetic acid, used for endoscope disinfection, also revealed improved prion decontamination. Animal assay demonstrated efficacy on TSE infectivity of H(2)O(2)/Cu alone or in combination with detergents (reduction factor > or =5.25 log(10)). Assays on classical pathogens confirmed the disinfection properties of the different processes. Taken together, these new disinfection processes are efficient for both conventional and prion infectious agents and are, compatible with thermosensitive medical equipment. They can be adapted to hospitals' and practitioners' routine use, and they present reduced risks for the environment and for healthcare professionals.