Anti-inflammatory treatment with acetylsalicylate or rofecoxib is not neuroprotective in Huntington's disease transgenic mice.
Inflammatory mechanisms have been implicated in the pathogenesis of Huntington's disease (HD). Possible benefits of anti-inflammatory treatments include improved folding of mutant huntingtin mediated through chaperones, reduction of destructive cellular and humoral inflammatory pathways, and reduction of proapoptotic signaling mediated by NF-kappaB or other transcription factors. This study was performed to investigate the therapeutic potential of anti-inflammatory drugs as treatments for Huntington's disease by examining whether two compounds in widespread human use can ameliorate the phenotype of HD transgenic mouse models. We examined the effectiveness of acetylsalicylate and rofecoxib as treatments for the R6/2 and N171-82Q transgenic mouse models of Huntington's disease. Both drugs were administered from weaning. To monitor the effectiveness of the treatment, we analyzed the mice for weight loss, behavioral changes, and gross cerebral and striatal atrophy. The studies showed that neither drug benefited the animals at doses comparable to those tolerated by humans.
Norflus
Fran
F
MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Nanje
Agnes
A
Gutekunst
Claire-Anne
CA
Shi
Geming
G
Cohen
Joshua
J
Bejarano
Michelle
M
Fox
Jonathan
J
Ferrante
Robert J
RJ
Hersch
Steven M
SM
D000161:Acoustic Stimulation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006816:Huntington Disease / Q000473:pathology* / Q000503:physiopathology*; D007783:Lactones / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009433:Neural Inhibition; D018696:Neuroprotective Agents / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology; D013216:Reflex, Startle / Q000187:drug effects; D013450:Sulfones
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D018696:Neuroprotective Agents; D013450:Sulfones; C116926:rofecoxib; D001241:Aspirin