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.
MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Fran
F
Norflus
Agnes
A
Nanje
Claire-Anne
CA
Gutekunst
Geming
G
Shi
Joshua
J
Cohen
Michelle
M
Bejarano
Jonathan
J
Fox
Robert J
RJ
Ferrante
Steven M
SM
Hersch
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