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Comment
. 2009 Jun;2(3):242-7.
doi: 10.1111/j.1752-8062.2009.00121.x.

Translational medicine lessons from flurizan's failure in Alzheimer's disease (AD) trial: Implication for future drug discovery and development for AD

Hong I Wan  1 , J Steve Jacobsen, J Lynn Rutkowski, Giora Z Feuerstein
Affiliations
Comment

Translational medicine lessons from flurizan's failure in Alzheimer's disease (AD) trial: Implication for future drug discovery and development for AD

Hong I Wan et al. Clin Transl Sci. 2009 Jun.
No abstract available

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Figures

Figure 1
Figure 1
Amyloid cascade hypothesis.
Figure 2
Figure 2
PK/PD analysis can be performed in multiple compartments across species.
Figure 3
Figure 3
Synthesis and clearance rate of amyloid‐β peptide can be measured in human CSF (adapted from Bateman et al., 25 with permission). (a) Diagram of an individual with an intravenous catheter in antecubital vein and a lumbar catheter in the L3–L4 intrathecal space.13C6‐labeled leucine was infused at a rate of 1.8–2.5 mg/kg/h for 9 or 12 hours after an initial bolus of 2 mg/kg. Plasma samples are collected through the other intravenous line and CSF samples through the lumbar catheter every hour, (b) Labeled leucine in the CSF and blood from an individual during a 36‐hour study. Labeled leucine in the CSF and plasma reaches a near steady‐state level within an hour. There was an exponential decay in labeled leucine levels after the infusion of leucine into the bloodstream was stopped at 9 hours, (c) The average labeled CSF Ab over 36 hours from six individuals. The labeled Ab curves were averaged and the mean for each time point is shown (±SEM). Each participant underwent labeling for 9 or 12 hours, whereas sampling occurred hourly from 0 to 12, 24, or 36 hours. There is no detectable incorporation of the label in the first 4 hours. This is followed by an increase in percent labeled Ab, which plateaus near the steady‐state levels of labeled leucine (approximately 10%), before decreasing over the last 12 hours of the study.
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References

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