Ksaales

3 Comments

    • ON: Tue May 13th 15:25 PM
      Commented on:
      Myriad Options on Alzheimers Disease
      Flurizan is not Flurbiprofen.
      Flurizan is R-flurbiprofen - the single enantiomer of the racemate NSAID flurbiprofen. Flurbiprofen has substantial anti-inflammatory activity through COX (because of S-flurbiprofen), R-flurbiprofen does not.

      www.pubmedcentral.nih....
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    • ON: Tue May 13th 12:15 PM
      Commented on:
      Myriad Options on Alzheimers Disease
      Gamma secretase modulation is not the only theoretical MOA of NSAIDS in AD, however it may be the only one that works. Flurizan does not claim an anti-inflammatory mechanism, particularly one through COX, so attempting to discredit Flurizan by touting evidence against an anti-inflammatory mechanism is twisting the evidence to support your short position.
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    • ON: Tue May 13th 11:39 AM
      Commented on:
      Myriad Options on Alzheimers Disease
      1. The effect of Flurizan is that it works in mild patients (2 out of 3 endpoints statistically significant in the phase 2 study) but there is no evidence of an effect in moderate patients. This is consistent with the quoted observation that "NSAIDs might exert protective effects only if given several years before the time when symptoms would otherwise develop." Earlier treatment is likely to be better than later treatment for a disease modifying drug. It is important to remember that the phase 2 study was a phase 2 study: designed to determine the appropriate dose and patient population and provide PRELIMINARY evidence of a drug effect. It accomplished all three of these objectives.
      2. The dose of Flurizan that shows the effect seen in the phase 2 study is 1600 mg/day. This dose of Ibuprofen and the other NSAIDS that have been shown to have an effect on abeta42 would not be tolerable for any reasonable amount of time. In addition, the mouse model and cell model data show that Flurizan is more potent than any of the NSAIDS that also modulate gamma secretase, so it is likely that even higher doses would be needed for Ibuprofen and other NSAIDS. It is only because Flurizan is not a significant inhibitor of Cox that it is able to be given at such high doses over such a long period of time.

      I agree with the first comment by Mudphud. This statement is completely misleading: "While this study does not mirror the Myriad study, it still gives valuable hints on the possible outcome. There were some hopes that anti-inflammatory compounds may have a role to play on the treatment of AD. It seems that is premature." This implies that Flurizan is working through an anti-inflammatory effect rather than a modulation of gamma secretase which these two compounds do not have. Only a subset of NSAIDS have this activity.

      I am also optimistic about Bapineuzumab, however the phase 2 data is not yet available, so it's easy to be optimistic. It is also important to realize that the safety issues of this compound may be substantial, and again, having no data makes it easier to remain optimistic.
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