Anti-inflammatory treatment with acetylsalicylate or rofecoxib is not neuroprotective in Huntington's disease transgenic mice

The use of the R6 transgenic mouse models of Huntington’s disease in attempts to develop novel therapeutic strategies

“…After treatments in the R6/2 mice, both drugs failed to show effects on survival, weight loss, and behavioral abnormalities. 135 However, another anti-inflammatory and antioxidant compound, BN82451, significantly, but transiently, improved Rotarod performance in R6/2 mice when given orally starting before the onset of symptoms. Onset of symptoms was postponed and survival extended for around 2 weeks.…”

The R6 lines of transgenic mice: A model for screening new therapies for Huntington's disease

“…Although no major signs of inflammation have been detected in R6 brains, the up-regulation of certain genes involved in inflammation (Luthi-Carter et al, 2000) and the activation of iNOS and caspase-1 (enzymes that are known to be involved in the inflammatory response) (Chen et al, 2000) have been reported to occur in R6/2 mice. Within this context, a recent study evaluated the potential therapeutic benefits of two commonly used anti-inflammatory drugs (acetylsalicylate and rofecoxib, inhibitors of cycloxygenases 1 and 2, respectively) in both N171-82Q and R6/2 transgenic mouse models of HD (Norflus et al, 2004). However, the administration of both drugs from weaning (at doses comparable to those tolerated by humans) had no significant effect on survival, behavioral changes, loss of body weight, or gross cerebral and striatal atrophy of both N171-82Q and R6/2 mice (Norflus et al, 2004), suggesting that inflammation is not a major contributor for the pathology of these mice.…”

“…Within this context, a recent study evaluated the potential therapeutic benefits of two commonly used anti-inflammatory drugs (acetylsalicylate and rofecoxib, inhibitors of cycloxygenases 1 and 2, respectively) in both N171-82Q and R6/2 transgenic mouse models of HD (Norflus et al, 2004). However, the administration of both drugs from weaning (at doses comparable to those tolerated by humans) had no significant effect on survival, behavioral changes, loss of body weight, or gross cerebral and striatal atrophy of both N171-82Q and R6/2 mice (Norflus et al, 2004), suggesting that inflammation is not a major contributor for the pathology of these mice.…”

An Overview of Target Specific Neuro-Protective and Neuro-Restorative Strategies

“…Treatment with acetylsalicylate or rofecoxib in transgenic mice model of HD failed to show any beneficial effects (Norfus et al, 2004). Dexamethasone treatment (4mg daily for 20 days followed by 8mg daily for an additional 20 days) in HD patients has demonstrated improvement of abnormal involuntary movements, and manual dexterity, with no observable side-effects (Bonnucelli et al, 1992).…”