Title

Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloid-β peptide and τ levels: target engagement, tolerability and pharmacokinetics in humans.

Journal

Journal of neurology, neurosurgery, and psychiatry

Volume

83

Issue

None

Pages

894-902

Date

2012-09-01

Authors

John V | Maccecchini ML | Zetterberg H | Greig NH | Pan C | Chang MY

A 160 mg dose was associated with an increased incidence of nausea and vomiting (four subjects were nauseous and three vomited)

Posiphen 80 mg was determined as the no observed adverse effect level (table 1).

Specifically, Posiphen lowered sAPPa and sAPPb levels by
59.9% and
57.7%, respectively, assessed by the AlpaLisa assay, and by
34.1% and
34%, respectively, assessed by the MSD assay, in accordance with Posiphen’s proposed mechanism of action to inhibit APP expression.

In addition, Posiphen significantly reduced levels of t-s (
74.1%, as assessed by the Innogenetics assay and
46.2%, as assessed by the AlphaLisa assay) and p-s (
61%, as assessed by the Innogenetics assay).

A significant lowering of pro-inflammatory, C3 (
86.9%) and microglial activation markers, MCP-1 (
87.5%) and YKL-40 (
72.7%), was evident.

and the complement control protein, factor H, were unaffected by Posiphen (
26.1% and +23.7%, respectively).

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