title: Evaluation of drugs for treatment of prion infections of the central nervous system.
abstract: Prion diseases are fatal and at present there are neither cures nor therapies available to delay disease onset or progression in humans. Inspired in part by therapeutic approaches in the fields of Alzheimer's disease and amyotrophic lateral sclerosis, we tested five different drugs, which are known to efficiently pass through the blood-brain barrier, in a murine prion model. Groups of intracerebrally prion-challenged mice were treated with the drugs curcumin, dapsone, ibuprofen, memantine and minocycline. Treatment with antibiotics dapsone and minocycline had no therapeutic benefit. Ibuprofen-treated mice showed severe adverse effects, which prevented assessment of therapeutic efficacy. Mice treated with low- but not high-dose curcumin and mice treated with memantine survived infections significantly longer than untreated controls (P<0.01). These results encourage further research efforts to improve the therapeutic effect of these drugs.
authors.affiliation: Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
authors.forename: Constanze
authors.initials: C
authors.lastname: Riemer
authors.affiliation: Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Burwinkel
authors.affiliation: Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schwarz
authors.affiliation: Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Gültner
authors.affiliation: Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
authors.forename: Simon W F
authors.initials: SWF
authors.lastname: Mok
authors.affiliation: Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Heise
authors.affiliation: Institute of Neuropathology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Nikola
authors.initials: N
authors.lastname: Holtkamp
authors.affiliation: Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Baier
mesh_terms: D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000401:mortality; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use; D005069:Evaluation Studies as Topic; D007052:Ibuprofen / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use; D017096:Prion Diseases / Q000188:drug therapy* / Q000401:mortality
chemical_list: D008911:Minocycline; D003474:Curcumin; D008559:Memantine; D007052:Ibuprofen