Evaluation of drugs for treatment of prion infections of the central nervous system.
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.
Riemer
Constanze
C
Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
Burwinkel
Michael
M
Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
Schwarz
Anja
A
Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
Gültner
Sandra
S
Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
Mok
Simon W F
SWF
Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
Heise
Ines
I
Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
Holtkamp
Nikola
N
Institute of Neuropathology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Baier
Michael
M
Project Neurodegenerative Diseases, Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
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
D008911:Minocycline; D003474:Curcumin; D008559:Memantine; D007052:Ibuprofen